Stephen H. Safe

STEPHEN H. SAFE

Distinguished Professor telephone: (979) 845-5988 Texas A&M University fax: (979) 862-4929 College Station, TX 77843-4466 email: [email protected]

EDUCATION: B.Sc., Queen's University, 1962 M.Sc., Queen's University, 1963 D. Phil., Oxford University, 1965

FIELDS OF SPECIALIZATION: Molecular Oncology Biochemistry Toxicology

ACADEMIC APPOINTMENTS AND PROFESSIONAL EXPERIENCE: Research Assistant, Oxford University, 1966 Research Associate, Harvard University, 1967 Associate Research Officer, National Research Council of Canada, 1968-73 Associate Professor, University of Guelph, Canada, 1973-77 Professor, University of Guelph, Canada, 1977-81 Distinguished Professor, Veterinary Physiology & Pharmacology, Texas A&M University, 1981-present Chester J. Reed Chair in Toxicology, 1983 Senior Scientist, Institute of Occupational & Environmental Medicine, Texas A&M University, 1983-present Distinguished Professor, Texas A&M University, 1984-Present Adjunct Professor, University of Guelph, 1985-Present Sid Kyle Chair in Toxicology, Texas A&M University, 1992 Director, Center for Environmental and Genetic Medicine, Institute of Biosciences & Technology, Texas A&M Health Science Center, 2002-present

PROFESSIONAL AND HONORARY SOCIETIES: American Association for Advancement of Science (AAAS) American Association for Cancer Research Endocrine Society FASEB Sigma Xi Society of Toxicology

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AWARDS, HONORS, AND LISTINGS: NSERC Research Scholarship, 1962 Commonwealth Scholarship, 1963-1966 Sigma Xi Award for Excellence in Research, 1977 Queen's Silver Jubilee Medal, 1978 Queen's University Quest Lecturer, 1980 Royal Society of Chemistry Award For Health, Safety or Environmental Chemistry, 1984 Distinguished Lecturer in oxicology Seminar Series, University of Nebraska Medical School, Omaha, 1986 Distinguished Achievement Award for Research, Texas A&M University, 1988 Burroughs Wellcome Toxicology Scholar, 1989 MillerComm Lecturer, University of Illinois, 1990 University Lecturer, Texas A&M University, 1991 Distinguished Scientist Award, Sigma Xi, Texas A&M University, 1995 Eli Lilly Science and Society Lecturer, Indiana State University, 1995 Charles W. Gowdy Distinguished Lecturer, University of Western Ontario, 1996 Samuel H. Kuna Distinguished Lecturer, Rutgers University, 1996 Honorary D.Sc., University of Guelph, 1996 McEwen Lecturer, Queen’s University, 1998 High Impact Environmental Research – Environmental Science and Technology, 2001 Highly Cited Research – Pharmacology and Ecology/Environment – ISI, Thomson Scientific, 2002 Spirit of Innovation Award, Technology Licensing Office, Texas A&M University, 2003 JoAnn Treat Research Excellence Award, Texas A&M Research Foundation, Texas A&M University, 2004 Regents Professor, Texas A&M University System, 2005 Texas A&M University Association of Former Students Award for Distinguished Research, 2006 Distinguished Lifetime Toxicology Scholar Award, Society of Toxicology, 2007 Spirit of Innovation Award, Technology Licensing Office, Texas A&M University, 2014

COMMITTEE EXPERIENCE: Chemical Institute of Canada (Chairman - Wellington Section), 1974 Departmental Promotion and Tenure, Library, Publicity, 1977-79 Guelph-Waterloo Centre Coordinating Committee, 1978-79 College - Promotion and Tenure Committee, 1978 University - Senate, Guelph-Toronto Toxicology Centre Committee, 1979-1981 Chairman, Toxicology Grants Committee- Health and Welfare, Canada, 1980-84 Environment Canada - Task Force on Hazardous Waste Definition, 1979 Panel Member, NRC Associate Committee on Scientific Criteria for Environmental Quality, Chlorinated Phenols, 1981 Panel Member, NRC Associate Committee on Scientific Criteria for Environmental Quality, Polychlorinated Dibenzo-p-dioxins; 1981 Ontario Ministry of the Environment - Dioxin Advisory Group, 1983-present Canadian Centre for Toxicology-Steering Committee, 1979-present Consultant, E.P.A. Environmental Criteria and Assessment Office,1983 Consultant, Science Advisory Board of E.P.A., 1984-present Member, National Advisory Environmental Health Sciences Council, 1984-1988 Senior Scholars Committee, Texas A&M University, 1984-1986 Chairman, Senior Scholar's Committee, Texas A&M University, 1986

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International Advisory Board, Dioxin Symposia, 1980-present President-Elect, Gulf Coast Society of Toxicology Chapter, 1986 Biochemistry Head Search Committee, Texas A&M University, 1987 Vice Chancellor Agriculture Search Committee, Texas A&M University, 1987 President, Gulf Coast Society of Toxicology, 1987 Education Committee, Society of Toxicology, 1989-1991 Associate Dean for Research, Search Committee, Texas A&M University, 1989-1990 Chairman Executive Committee, Faculty of Toxicology, Texas A&M University, 1989-present Provost and Vice President, Academic Search Committee, 1990 Scientific Advisor, Texas Air Control Board, 1990 Promotion and Tenure Committee, Department of Veterinary Physiology and Pharmacology, 1991-1995 Chair, Education Committee, Society of Toxicology, 1991 Promotion and Tenure Committee, Biochemistry Department, Texas A&M University, 1992 Department Head Search Committee, Biochemistry Department, Texas A&M University, 1992 External Advisory Board - Environmental Health Center, University of California-Davis, 1992- 1977 External Advisory Board - Marine and Freshwater Biomedical Sciences Center, University of Miami,1991-1995 External Advisory Board, Environmental Health Center, University of Texas, 1995-present Member, NRC Committee on Hormonally-Active Agents in the Environment, 1995-1996 Member, Institute of Medicine Committee on Gender Differences in Susceptibility to Environmental Factors, 1997 Member, EDSTAC Working Group, US EPA, 1997 Member, College of Veterinary Medicine Dean Search Committee, 1997 Councilor, Society of Toxicology, 1997 Member, Life Sciences Task Force, Texas A&M University, 1999-2001 Member, Scientific Advisory Board, Avax Technologies, Kansas City, 1998-2003 Member, University Fellows Selection Committee, 2000-2001 Member, Scientific Advisory Committee on Alternative Toxicological Testing Methods, NIEHS, 2002-present Member, Society of Toxicology Awards Committee, 2003-2005 Chair, Society of Toxicology Awards Committee, 2003 Member, Advisory Committee (SACATM) for the National Toxicology Program, 2004-2007 Scientific Advisory Board, Plantacor, 2004-present Scientific Advisory Board, Meharry Medical University - Vanderbilt University ARCH Consortium, Nashville, TN, 2007-present Member, Vice-President for Research Search Committee, Texas A&M University, 2008-2009 Member, Dean Search Committee, College of Veterinary Medicine, Texas A&M University, 2008-2009 Member, Associate Vice President for Graduate Studies Search Committee, Texas A&M University, 2010 Member, Continuing Education Committee, Society of Toxicology, 2009-present Scientific Advisory Board, Scientific and Prevention Advisory Council (SPAC) of the Cancer Prevention and Research Institute of Texas (CPRIT), 2009-2010 Chair, Oncology Fellowship Study Section, National Cancer Institute - NIH Member, Peer Review Committee, Susan G. Komen for the Cure's Targeted Therapies, 2009-2011 Chair, Xenobiotic and Nutrient Disposition and Action (XNDA) Study Section, NIH, 2011- 2014

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Chair, Department of Veterinary Physiology & Pharmacology Promotion and Tenure Committee, 2012-present Member, College of Veterinary Medicine & Biomedical Sciences Promotion and Tenure Committee, 2012-present Member, Texas A&M University Institute for Advanced Study (TIAS) Advisory Board, 2012- present

SCIENTIFIC EDITORIAL RESPONSIBILITIES: Associate Editor: BioMed Research International Editorial Board: Clinical Pharmacology: Advances and Applications, Journal of Biological Chemistry, Journal of Women's Cancer, Breast Cancer: Targets and Therapy, Nutrition and Dietary Supplements, Reactive Oxygen Species

CONSULTATIVE EXPERIENCE: Numerous government agencies, industrial companies, environmental groups and citizens

AREAS OF RESEARCH INTEREST: AhR as a drug target for cancer chemotherapy Drugs that taraget NR4A receptors for cancer chemotherapy Sp transcription factors: non-oncogene addiction genes and drug targets Molecular biology of endocrine disrupting chemicals Mechanisms of microbiota impact on gut health

COMMUNITY/CIVIC ACTIVITIES: Numerous hearings and court appearances for civic groups regarding environmental problems; television, magazine, radio and newspaper commentaries on scientific/toxicologic issues Various church and young people's activities

TITLES OF THESIS AND/OR DISSERTATION: The Ullmann Reaction (Thesis) Polyacetylenes from Dahlia (Dissertation)

TECHNOLOGY TRANSFER:

1. Disclosures of Invention

"Applications and Synthesis of Polyalkyl-substituted Dibenzofurans as Antitumorigenic Agents," TAMUS 1624.

"Target Degradation of Sp Proteins by NSAIDs/COX-2 Inhibitors for Inhibition of Cancer Cell Growth and Angiogenesis," TAMUS 2215.

"1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes as Activators of the Nuclear Orphan Receptors DAX and SHP," TAMUS 2249.

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"1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes and Ring-substituted DIMs Induce Cancer Cell Death Through Receptor-independent Pathways," TAMUS 2263.

"Tolfenamic Acids and Related NSAIDs as Inhibitors of Cancer Cell Growth and Angiogenesis through Targeted Degradation of Sp Proteins".

"Synthetic Glycyrrhetinic Acid Derivatives as a New Class of Anticancer Drugs".

"Anticancer Activity Through Targeting Sp Protein Degradation: Betulinic Acid". TAMUS 2429.

"Anticancer Activity Through Targeting a MicroRNA" (Track Code 2554HSC07) (9/6/2013)

"Development of Drugs to Target 1-Integrin in Cancer Cells and Tumors". TAMUS 3938 (10/9/2013)

"Botanical Isolates for Intestinal Health". TAMUS 4017 (4/15/2014) (Lead Investigator: Bhimanagouda S. Patil)

"Development of Drugs to Target PAX3-FOXO1A in Rhabdomyosarcoma (RMS)". TAMUS 4324 (7/15/2015)

2. Patent Applications

"Alkyl PCDFs as Treatment for Prostate Cancer," and "Alternate-Substituted Alkyl Polychlorinated Dibenzofurans (PCDF's)," U.S. Application # 20050143450 (June 30, 2005) and Foreign Patents Filed & Pending (TAMUS 1896).

"Inhibition of Atherosclerosis by Diindolylmethane Analogs," U.S. Application # 20060079568 (April 13, 2006) and Foreign Patents Filed & Pending (TAMUS 2117).

"Ligand-Dependant Activation of Nur77 and Uses Thereof," U.S. Application # 20060084694 (April 20, 2006) & Foreign Patents Filed & Pending (TAMUS 2167).

"Uses of Diphenyl/Diphenylamine Carboxylic Acids," U.S. Application # 20080261911 (October 23, 2008).

"Betulinic Acid, Derivatives and Analogs Thereof and Uses Therefor," U.S. Application # 20090203661 (August 13, 2009).

"Cancer Treatment Targeting Non-coding RNA Overexpression," U.S. Application # 20130267575 (October 10, 2013).

"Inhibitors of beta1-Integrin and Methods of Use," U.S. Application 61/149,289 (April 17, 2015), TAMUS 153816.

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3. Patents

"Synthesis and Application of Alkyl Substituted Dibenzofurans and Antitumorigenic Agents," U.S. Patent # 5,516,790 (TAMUS 0339).

"Indole-3-Carbinol, Diindolylmethane and Substituted Analogs as Antiestrogens," U.S. Patent # 5,948,808; European Patent # 0971890; German Patent # 69809726.2-08 (TAMUS 1152).

"Endocrine Therapy for Breast Cancer: Combined Treatment with Tamoxifen Plus Alkyl PCDFs," U.S. Patent # 6,136,845; Australian Patent # 772920; European Patent # 1140047; German Patent # 69912477.8-08 (TAMUS 1282).

"Compositions Containing C-Substituted Diindolymethane Compounds," U.S. Patent # 7,232,843 (June 19, 2007) and Foreign Patents Filed & Pending (TAMUS 1432/1495).

"Diindolylmethane and C-Substituted Diindolylmethane Compositions and Methods for the Treatment of Multiple Cancers," U.S. Patent # 7,709,520 (May 4, 2010).

"Antisense microRNA and Uses Therefor", U.S. Patent # 7,812,003 (October 12, 2010).

“C-Substituted Diindolylmethane Compositions and Methods for the Treatment of Multiple Cancers”, U.S. Patent # 8,389,563 (March 5, 2013). (1495AGLR99-08)

“Glycyrrhetinic Acid Derivatives”, U.S. Patent # 8,389,573 (March 5, 2013). (2771HSC08- 06)

“Use of Diindolylmethane (DIM) Compounds and Derivatives Neuroprotective Agents”, U.S. Patent # 8,580,843 (November 12, 2013). (3143AGLR10-01)

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RESEARCH PROJECTS ONGOING OR COMPLETED DURING THE LAST 3 YEARS:

Ongoing

P30-ES023512 (PI: Walker) 02/01/14 - 01/31/17 1.2 calendar NIEHS $0 ($600,000/yr) Center for Translational Environmental Health Research The objectives are to: 1) Build programmatic and scientific capacity for environmental health science research through member participation in Thematic Focus Areas and utilization of the Integrated Health Sciences Facility Core (IHFSC); 2) Integrate investigators with different expertise, support acquisition of new expertise by Center members and the development of promising new investigators in environmental health sciences through the Career Development Program; 3) Enhance the capabilities of existing programs in environmental health sciences through Facility Core resources and the Pilot Project Program; 4) Serve as a resource for information and expertise to surrounding communities, stakeholders, and Center members to further scientific collaborations and dissemination of research results through its Community Outreach and Engagement Core (COEC).

R21-ES025839 (PI: Safe) 08/01/15 – 07/31/17 1.2 calendar NIEHS $275,000 (2 yr) Cytosolic Ah Receptor: Mechanism of Action The discovery that the aryl hydrocarbon receptor (AhR) binds a vast array of ligands including endogenous biochemicals, phytochemicals and pharmaceuticals have led to discoveries showing the important roles of the AhR in cellular homeostasis and multiple diseases including cancer. We have identified AhR ligands that inhibit invasion of the most virulent sub-type of pancreatic cancer cells through the cytosolic and not the nuclear AhR, and the mechanism of cytosolic AhR action will be investigated in the proposed research.

Completed (During the Last 3 Years)

DOD – Breast Cancer Idea: BC095260 (Safe) 03/01/10 – 02/28/12 Novel Drugs That Target ErbB2 Betulinic acid (BA) and CDODA-Me will be used as model compounds to investigate the overall mechanism of BA-induced downregulation of ErbB2 and ErbB2 signaling in BT474 and SKBR3 breast cancer cell lines.

NCI: CA124998 (Role: PI) 11/01/07 - 10/31/12 Nur77 Agonists: New Targets for Pancreatic Cancer Chemotherapy This project investigated the mechanism of action of Nur77-active methylene-substituted diindolylmethanes (C-DIMs) in pancreatic cancer and their applications for cancer chemotherapy.

R01-CA136571 (Role: PI) 06/03/09 – 04/30/14 1.2 calendar National Cancer Institute $166,000 MicroRNAs as Targets for Colon Cancer Chemotherapy This project will focus on the mechanisms of action of betulinic acid, methyl 2-cyano-3,11-dioxo- 18-olean-1,12-dien-30-oate (CDODA-Me), and tolfenamic acid with emphasis on their effects on the oncogenic microRNA-27a (miR-27a) and other miRs and the role in repression of Sp proteins and other critical genes.

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W81XWH-11-1-0211 (Role: Co-PI) 04/01/11 – 03/31/15 0.6 calendar DOD – Partnership Training Award The Role of Novel Substituted Diindolylmethane Analogs in the Treatment of Triple Negative Breast Cancer This project will involve mentoring and research on development of new mechanism-based anticancer drugs. (PI: M. Sancheva, FAMU)

R01-CA142697 (Role: PI) 07/01/10 – 06/30/15 1.2 calendar National Cancer Institute Molecular Mechanisms and Application of Ah Receptor-MicroRNA Interactions These studies will characterize the molecular mechanisms of AhR-miR interactions and development of SAhRMs for clinical applications in the treatment of ER-negative breast cancer.

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SCIENTIFIC PUBLICATIONS:

Refereed

1. Safe, S., Allen, M., and Moir, R.Y. Metameconine as a model compound in the study of aromatic reactions. Can. J. Chem. 40:2402-2408, 1962. 2. Safe, S. and Moir, R.Y. Sterochemical configuration of some phthalideisoquinoline alkaloids. Can. J. Chem. 42:160-162, 1964. 3. Safe, S. and Moir, R.Y. A series of model compounds for the study of aromatic reactions. Can. J. Chem. 43:337-342, 1965. 4. Jones, E.R.H., Safe, S. and Thaller, V. Natural acetylenes. Part XXIII. A C18 polyacetylenic ketoaldehyde related to falcarinone from an umbellifer (Pastinaca sativa L.). J. Chem. Soc. (C):1220-1221, 1966. 5. Aplin, R.T. and Safe, S. Electron impact-induced rearrangements of natural polyacetylenes. Chem. Comm. 140-142, 1967. 6. Jones, E.R.H., Safe, S. and Thaller, V. Natural acetylenes. Part XXVI. Transformations of phenylpolyacetylenes in the tubers of dahlia hybrids. J. Chem. Soc. (C):1038-1041, 1967. 7. Aplin, R.T., Durham, L.J., Kanazawa, Y. and Safe, S. 2-0-α-D-Galactopyranosylglycerol from Laurencia pinnatifida. J. Chem. Soc. (C):1346-1347, 1967. 8. Brewer, D., Rahman, R., Safe, S. and Taylor, A. A new toxic metabolite of pithomyces chartarum related to the sporidesmins. Chem. Comm. 1571, 1968. 9. Safe, S. and Taylor, A. Stereochemistry of the reaction of epipolythiadioxopiperazines with triphenylposphine. Chem. Comm. 1466-1467, 1969. 10. Rahman, R., Safe, S. and Taylor, A. Sporidesmins. Part IX. Isolation and structure of Sporidesmin. E. J. Chem. Soc. (C):1665-1668, 1969. 11. Safe, S. Hydrogen randomization between phenyl groups in the electron impact-induced fragmentation of substituted diphenylacetylenes. Chem. Comm. 534-535, 1969. 12. Aplin, R.T. and Safe, S. Electron impact-induced rearrangements of acetylenic compounds. Can. J. Chem. 47:1599-1601, 1969. 13. Safe, S., Jamieson, W.D., Pilgrim, W.R. and Wolfe, S. Electron impact-induced rearrangements of substituted 1-phenylpropynes. Can. J. Chem. 48:1171-1174, 1970. 14. Safe, S. Preparation of iodobenzene-d5 and diphenylacetylene-d5. J. Label. Cpds. 6:197-198, 1970. 15. Safe, S. and Taylor, A. Sporidesmins. Part X. Synthesis of polysulphides by reaction of dihydrogen disulphide with disulphides and thiols. J. Chem. Soc. (C):432-435, 1970. 16. Chin, C., Cutler, M.C., Jones, E.R.H., Lee, J., Safe, S. and Thaller, V. Natural acetylenes. Part XXXI. C14-Tetrahydropyranyl and other polyacetylenes from the compositae Dahlia coccinea cav. var. Coccinea. J. Chem. Soc. (C):314-322, 1970. 17. Safe, S. Timing of hydrogen randomization in substituted diphenyl acetylenes. Org. Mass. Spectrom. 3:239-240, 1970. 18. Rahman, R., Safe, S. and Taylor, A. Separation of polythiadioxopiperazine antibiotics by thin-layer chromatography. J. Chromatog. 53:592-594, 1970. 19. Idler, D.R., Safe, L.M. and Safe, S.H. Mass spectrometric studies of methyl ether derivatives of sterols. Steroids 1 6:251-262, 1970. 20. Rahman, R., Safe, S. and Taylor A. The stereochemistry of polysulphides. J. Chem. Soc. 24:208-237, 1970. 21. Safe, S. and Taylor, A. Sporidesmins. Part XI. The reaction of triphenylphosphine with epipolythio-dioxopiperazines. J. Chem. Soc. (C):1189-1192, 1971. 22. Safe, S. Mass spectra of aromatic and acetylenic compounds. Part VI. The electron

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impact-induced rearrangements of substituted phenylacetylenes. J. Chem. Soc. (B):962-965, 1971. 23. Marchelli, R., Jamieson, W.D., Safe, S.H., Hutzinger, O. and Heacock, R.A. Mass spectra of the hydroxyindole-3-carboxylic acids and the hydroxyskatoles. Can. J. Chem. 49:1296-1300, 1971. 24. Safe, S. and Hutzinger, O. Chlorine randomization between phenyl groups in the electron impact-induced fragmentation of polychlorinated biphenyls. Chem. Comm. 446-448, 1971. 25. Hutzinger, O., Jamieson, W.D. and Safe, S. Mass spectra of fifteen chlorinated aromatic fungicides. J. Assoc. Offic. Anal. Chem. 54:178-186, 1971. 26. Zitko, V., Hutzinger, O. and Safe, S. Retention times and electron-capture detector responses of some individual chlorobiphenyls. Bull. Environ. Contam. and Toxicol. 6:160-163, 1971. 27. Safe, S. and Penney, C. Preparation of cis- and trans-α-d-3-aklenoic acids. J. Label. Cpds. 7:341-343,1971. 28. Safe, S. and Hutzinger, O. Polychlorinated biphenyls: photolysis of 2,4,6,2’,6’- hexachlorobiphe-nyl. Nature 232:641-642, 1971. 29. Safe, S. Electron-impact induced rearrangements of substituted biphenyls. Org. Mass. Spect. 5:1221-1226, 1971. 30. Hutzinger, O., Jamieson, W.D. and Safe, S. Mass spectra of some fungicidal organomercury compounds. Intern. J. Environ. Anal. Chem. 1:85-97, 1971. 31. Hutzinger, O., Safe, S. and Zitko, V. Polychlorinated biphenyls: synthesis of some individual chlorobiphenyls. Bull. Environ. Contam. Toxicol. 6:209-219, 1971. 32. Wallnofer, P., Safe, S. and Hutzinger, O. Metabolism of the systemic fungicide 2- methylbenzanilide and 2-chlorobenzanilide by Rhizopus japonicus. Pesticide Biochem. Hysiol. 1:458-463, 1971. 33. Francis, E., Rahman, R. Safe, S. and Taylor, A. Sporidesmins. Part XII. Isolation and structure of sporidesmin G, a naturally-occurring 3,6-epitetrathiopeperazine-2,5-dione. J. Chem. Soc. Perkin 18:470-472, 1972. 34. Safe, S. and Taylor, A. Sporidesmins. Part XIII. Ovine ill-thrift in Novia Scotia. 3. The characterization of chetomin, a toxic metabolite of Chaetomium cochliodes and Chaetomium globosum. J. Chem. Soc. Perkin 18:472-479, 1972. 35. Brewer, D., Duncan, J.M., Safe, S. and Taylor, A. Part XIII. Ovine ill-thrift in Nova Scotia. 4. The survival at low oxygen partial pressure of fungi isolated from the contents of ovine rumen. Can. J. Microbiol. 18:1119-1128, 1972. 36. Brewer, D., Duncan, J.M., Jerram, W.A., Leach, C.K., Safe, S., Taylor, A. and Vining, L.C. Part XIII. Ovine ill-thrift in Nova Scotia. 5. The production and toxicology of chemotin a metabolite of Chaetomium spp. Can. J. Microbiol. 18:1129-1137, 1972. 37. Wright, J.L.C., Jamieson, W.D., Safe, S. and Vining, L.C. Mass spectra of some tropolones and tropolone methyl ethers. Can. J. Chem. 50:821-825, 1972. 38. Atherton, L., Duncan, J.M. and Safe, S. Isolation and biosynthesis of ergosta- 5,7,9(11),22-tetraen-3β-ol from Mucor rouxii. Chem. Comm. 882-883, 1972. 39. Safe, S., Jamieson, W.D. and Hutzinger, O. The ion kinetic energy and mass spectra of isomeric methyl indoles. Org. Mass Spect. 6:33-37, 1972. 40. Safe, S. and Hutzinger, O. The mass spectra of polychlorinated biphenyls. J. Chem. Soc. Perkin I:686-691, 1972. 41. Hutzinger, O., Safe, S. and Zitko, V. Photochemical degradation of chlorobiphenyls. Environ. Health Perspect. 1:15-21, 1972. 42. Hutzinger, O. and Safe, S. A general method for the preparation of tritiated polychlorobiphenyls of high specific activity: 2,2’,5,5’,-tetrachlorobiphenyl-[3H] and 2,2’,4,4’,5,5’-hexachlorobiphenyl- [3H]. Bull. Environ. Contam. Toxicol. 7:374, 1972.

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43. Safe, S., Hutzinger, O. and Cook, M. The ion kinetic energy and mass spectra of the isomeric mono- and di-choronaphthalenes. Chem. Comm., 260-262, 1972. 44. MacNeil, J.D., Frei, R.W., Safe, S. and Hutzinger, O. Electron-donor-acceptor complexing reagents in the analysis of pesticides. V. Analysis of pesticide decomposition products via electron-donor-acceptor complexes; photolysis of methoxychlor. J. Assoc. Offic. Anal. Chem. 55:1270-1275, 1972. 45. Hutzinger, O., Safe, S. and Zitko, V. Analysis of chlorinated aromatic hydrocarbons by exhaustive chlorination. Quantitative and structural aspects of perchloroderivatives of biphenyl, naphthalene, terphenyl, dibenzofuran, dibenzodioxin and DDE. Environ. Anal. Chem. 2:95-106, 1972. 46. Hutzinger, O., Pothier, C. and Safe, S. Synthesis of chlorobiphenyls labeled with deuterium and chlorine-36. J. Assoc. Offic. Anal. Chem. 55:753-756, 1972. 47. Wallnofer, P., Koniger, M., Safe, S. and Hutzinger, O. The metabolism of the systemic fungicide carboxin (vitavax) by Rhizopus japonicus. Intern. J. Environ. Anal. Chem. 2:37-43, 1972. 48. Wallnofer, P.R., Koniger, M., Safe, S. and Hutzinger, O. Metabolism of the systemic fungicide 2,5-dimethyl-3-furancarboxylic acid anilide (BAS 3191) by Rhizopus japonicus and related fungi. J. Agr. Food Chem. 20:20-22, 1972. 49. Wallnofer, P.R., Safe, S. and Hutzinger, O. Die hydroxylation des herbazids karsil [N- (3,4-dichlorophenyl)-2-methylpentan-amid)] durch Rhizopus japonicus. Chemosphere 1:155-158, 1972. 50. Hutzinger, O., Nash, D.M., Safe, S., DeFreitas, A.S.W., Norstrom, R.J., Wildish, D.J. and Zitko, V. Polychlorinated biphenyls: Metabolic behavior of pure isomers in pigeons, rats and brook trout. Science 178:312-314, 1972. 51. Ackman, R.G., Safe, L., Hooper, S.N., Paradis, M. and Safe, S. 7-Methyl-7- hexadecenoic acid. Isolation from lipids of the ocean sunfish Mola Mola (Linnaeus) 1758. Lipids 8:21-24, 1973. 52. Safe, S. and Brewer, D. Lipid composition of Chaetomium cochliodes: effect of media. Lipids 8:311-314, 1973. 53. Przybylska, M., Gopalakrishna, E.M., Taylor, A. and Safe, S. X-ray crystallographic determination of the stereochemistry of the tetrathio bridge in sporidesmin G. Chem. Comm. 554-555, 1973. 54. Safe, S. The effect of environment on the free and hydrosoluble sterols of Mucor rouxii. Biochem. Biophys. Acta 326:471-475, 1973. 55. Safe, S. Substituent and h/d randomization in the mass spectra of substituted diphenylacetylenic compounds. Org. Mass. Spectrom. 7:1329-1336, 1973. 56. Safe, S., Hutzinger, O. and Jamieson, W.D. The ion kinetic energy spectra of some chlorinated insecticides. Org. Mass Spectrum. 7:217-224, 1973. 57. Safe, S., Hutzinger, O. and Jamieson, W.D. The ion kinetic energy spectra of isomeric chlorobenzenes and polychlorinated biphenyls (PCB's). Org. Mass Spectrom. 7:169- 176, 1973. 58. Hutzinger, O., Safe, S., Wentzell, B.R. and Zitko, V. Photochemical degradation of di- and octachlorodibenzofuran. Environ. Health Persp. 5:267-271, 1973. 59. Hutzinger, O., Jamieson, W.D., Safe, S. and Zitko, V. Exhaustive chlorination as a technique in the analysis of aromatic hydrocarbons. J. Assoc. Offic. Anal. Chem. 56:1982-986, 1973. 60. Wallnofer, P.R., Safe, S. and Hutzinger, O. Microbial demethylation and debutyhylation of four phenylurea herbicides. Pest. Biochem. Physiol. 3:253-258, 1973. 61. Wallnofer, P.R., Safe, S. and Hutzinger, O. Microbial hydroxylation of the herbicide N- (3,4-dichlorophenyl)-methacrylamide (dicryl). J. Agr. Fd. Chem. 21:502-504, 1973. 62. Wallnofer, P.R., Engelhardt, G., Safe, S. and Hutzinger, O. Microbial hydroxylation of 4-

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chlorobiphenyl and 4,4’-dichlorobiphenyl. Chemosphere 2:69-72, 1973. 63. Safe, S. and Duncan, J. Effect of oxygen levels on the fatty acids and lipids of Mucor rouxii. Lipids 9:285-289, 1974. 64. Safe, S. and Caldwell, J. The effect of growth environment on the free and hydrosoluble cell wall and cytoplasm lipid levels of Mucor rouxii. Can. J. Microbiol. 21:79-84, 1974. 65. Morris, D.C., Safe, S. and Subden, R.E. Detection of the ergosterol and episterol isomers lichesterol and fecosterol in nystatin-resistant mutants of Neurospora crassa. Biochemical Genetics 12:459-466, 1974. 66. Safe, S. Free and bound fatty acids from Mucor rouxii. The effect of thermal changes in the growth environment and the age of cells. Lipids 9:952-956, 1974. 67. Hutzinger, O., Safe, S. and Zitko, V. Preparation, gas chromatography behavior, and spectroscopic properties of hydroxyalated chlorobiphenyls. J. Assoc. Offic. Anal. Chem. 57:1061-1067, 1974. 68. Safe, S., Jamieson, W.D. and Embree, D. The ion kinetic energy spectra of benzyl fluoride and the isomeric fluorotoluenes. Can. J. Chem. 52:867-869, 1974. 69. Hutzinger, O., Safe, S. and Heacock, R.A. Chlorobiphenylols: thin-layer chromatographic and colour reactions of some hydroxylated chlorobiphenyls. J. Chromatog. 97:233-247, 1974. 70. Hutzinger, O., Jamieson, W.D., Safe, S., Paulmann, L. and Ammon, R. Identification of metabolic dechlorination of highly chlorinated biphenyl in rabbit. Nature 252:698-699, 1974. 71. Safe, S., Hutzinger, O. and Ecobichon, D. Identification of 4-chloro-4-hydrobiphenyl and 4,4’-dichloro-3-hydroxybiphenyl as metabolites of 4-chloro- and 4,4’-dichlorobiphenyl fed to rats. Experientia 30:720-721, 1974. 72. Safe, S. and Safe, L.M. The isolation and synthesis of E-24-ethylidene-5α-lanost-8-en- 3β-yl acetate. Can. J. Chem. 53:3247-3248, 1975. 73. Safe, S., Safe, L.M. and Maass, W.S.G. Sterols of three lichen species: Lobaria pulmonaria, Lobaria scrobiculata and Usnea longissima. Phytochemistry 14:1821-1823, 1975. 74. Ruzo, L.O., Bunce, N.J. and Safe, S. Photoreactions of simple halonaphthalenes in solution. Can. J. Chem. 53:688-693, 1975. 75. Safe, S., Jamieson, W.D., Hutzinger, O. and Poland, A.E. Mass and ion kinetic energy spectra of some chlorinated dibenzo-p-dioxins. Anal. Chem. 47:327-329, 1975. 76. Ruzo, L.O., Safe, S. and Zabik, M.J. Photodecomposition of unsymmetrical polychlorobiphenyls. J. Agr. Food Chem. 23:594-595, 1975. 77. Bunce, N.J., Safe, S. and Ruzo, L.O. Photochemistry of bromobiphenyls: steric effects and electron transfer. J. Chem. Soc., Perkin I:1607-1610, 1975. 78. Sundstrom, G., Safe, S. and Hutzinger, O. Polychlorinated biphenyls. Chem. Weekbld. 71:9, 1975. 79. Ruzo, L.O., Bunce, N.J., Safe, S. and Hutzinger, O. Photodegradation of polychloro- naphthalenes in methanol solution. Bull. Environ. Contam. Toxicol. 14:341-345, 1975. 80. Jones, D.H., Platonow, N.S. and Safe, S. Contamination of agricultural products by halogenated biphenyls. Can. Vet. J. 16:349-356, 1975. 81. Safe, S., Platonow, N., Hutzinger, O. and Jamieson, W.D. Analysis of organochlorine metabolites in crude extracts by high resolution photoplate mass spectrometry. Biomed. Mass Spectrom. 2:201-203, 1975. 82. Safe, S., Hutzinger, O., Ecobichon, D.J. and Grey, A.A. The metabolism of 4’-chloro-4- biphenylol in the rat. Can. J. BioChem. 53:415-420, 1975. 83. Safe, S., Platonow, N.S. and Hutzinger, O. Metabolism of chlorobiphenyls in the goat and cow. J. Agr. Food. Chem. 23:259-261, 1975. 84. Ruzo, L.O., Safe, S., Hutzinger, O., Platonow, N. and Jones, D. Hydroxylated

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metabolites of chloronaphthalenes (Halowax 1031) in pig urine. Chemosphere 121- 123, 1975. 85. Safe, S., Ruzo, L.O., Jones, D., Platonow, N.S. and Hutzinger, O. The metabolism of 4- chlorobiphenyl in the pig. Can. J. Physiol. Pharmacol. 53:392-396, 1975. 86. Safe, S., Hutzinger, O. and Jones, D. The mechanism of chlorobiphenyl metabolism. J. Agr. Food Chem. 23:851-853, 1975. 87. Safe, S. and Caldwell, J. The effect of growth environment on the chloroform-methanol and alkali-extractable cell wall and cytoplasm lipid levels of Mucor rouxii. Can. J. Microb. 21:79-84, 1975. 88. Renaud, R., Safe, S. and Subden, R. Free and bound lipids from Neurospora crassa. Phytochemistry 15:977-980, 1976. 89. Kohli, J., and Safe, S. The metabolism of brominated aromatic compounds. Chemosphere 5:433-437, 1976. 90. Safe, S., Jones, D., Kohli, J., Ruzo, L.O., Hutzinger, O. and Sundstrom, G. The metabolism of chlorinated aromatic pollutants by the frog. Can. J. Zool. 54:1818-1826, 1976. 91. Safe, S. and Caldwell, J. In vitro binding of sterols by extracts from Mucor rouxii cells grown under different environmental conditions. Can. J. Microb. 22:1163-1168, 1976. 92. Bedford, C.T., Bhattacharjee, D., Fairbrother, J.R.F., Jones, Sir E.R.H., Safe, S. and Thaller, V. Natural acetylenes. Part XLIX. Polyacetylenes from Dahlia scapigera (A. Dietr.) link and otto var. scapigera f. scapigera and some Dahlia hybrids. J. Chem. Soc. Perk. I:735-741, 1976. 93. MacNeil, J.D., Safe, S. and Hutzinger, O. The ultraviolet absorption spectra of some chlorinated biphenyls. Bull. Environ. Contam. Toxicol. 15:66-72, 1976. 94. Hutzinger, O., Sundstrom, G. and Safe, S. Environmental chemistry of flame retardants. Part I. Introduction and principles. Chemosphere, 3-10, 1976. 95. Ruzo, L.O., Sundstrom, G., Hutzinger, O. and Safe, S. Photodegradation of polybromobiphenyls (PBB). J. Agr. Food Chem. 24:1062-1065, 1976. 96. Sundstrom, G., Hutzinger, O. and Safe, S. The identification of 2,2’,4,4’,5,5’- hexabromobiphenyl as the major component of the flame retardant FireMaster BP-6. Chemosphere, 11-14, 1976. 97. Sundstrom, G., Hutzinger, O., Safe, S. and Zitko, V. The synthesis and gas chromatographic properties of bromobiphenyls. Sci. Total Environ. 6:15-29, 1976. 98. Ruzo, L.O., Sundstrom, G., Hutzinger, O. and Safe, S. Environmental chemistry of PCB replacement compounds. II. Photochemical properties of aklylchlorobiphenyls. Chemosphere 71-76, 1976. 99. Ruzo, L.O., Sundstrom, G., Safe, S. and Hutzinger, O. Fotochemische reakties van milieuvreemde stoffen. Chemisch Weekblad. August:420-423, 1976. 100. Safe, S., Ellis, B.E. and Hutzinger, O. The in vitro hydroxylation of 4’-chloro-4-biphenylol by a mushroom tyrosinase preparation. Can. J. Microbiol. 22:104-106, 1976. 101. Maass, W.S.G., Hutzinger, O. and Safe, S. Metabolism of 4-chlorobiphenyl by lichens. Arch. Environ. Contam. Toxicol. 3:470-478, 1976. 102. Crocker, J.F.S., Ozere, R.L., Safe, S.H., Digout, S.C., Rozee, K. and Hutzinger, O. Lethal interaction of ubiquitous insecticide carrier with virus. Science 192:1351-1353, 1976. 103. Ruzo, L.O., Jones, D., Safe, S. and Hutzinger, O. Metabolism of chlorinated naphthalenes. J. Agr. Food Chem. 24:581-583, 1976. 104. Ruzo, L.O., Safe, S., Jones, D. and Platonow, N. Uptake and distribution of chloronaphthalenes and their metabolites in pigs. Bull. Environ. Contam. Tox. 16:233- 239, 1976. 105. Rogers, A., Mellors, A. and Safe, S. Lysosomal membrane labilization by DDT, DDE

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and polychlorinated biphenyls (PCB). Res. Commun. Chem. Pathol. Pharmacol. 13:341-344, 1976. 106. Ruzo, L.O., Safe, S. and Hutzinger, O. Metabolism of bromobenzenes in the rabbit. Agr. Food Chem. 24:291-293, 1976. 107. Sundstrom, G., Hutzinger, O. and Safe, S. The metabolism of chlorobiphenyls - a review. Chemosphere 5:267-298, 1976. 108. Kohli, J., Jones, D. and Safe, S. The metabolism of higher chlorinated benzene isomers. Can J. BioChem. 54:203-208, 1976. 109. Sundstrom, G., Hutzinger, O. and Safe, S. The metabolism of 2,2',4,4',5,5'- hexachlorobiphenyl by rabbits, rats and mice. Chemosphere 4:249-253, 1976. 110. Sundstrom, G., Olie, K., Hutzinger, O., Chittim, B. and Safe, S. Composition and photochemistry of Iralec. Chemosphere 6:103-108, 1977. 111. Chittim, B. and Safe, S. Photodecomposition of 2,5-dichloro-p-terphenyl, 2,4,6-trichloro- p-terphenyl and 2,5-dichloro-o-terphenyl in solution. Chemosphere 6:269-277, 1977. 112. Safe, S., Plugge, H. and Crocker, J.F.S. Analysis of an aromatic solvent used in a forest spray program. Chemosphere 6:641-651, 1977. 113. Crawford, A. and Safe, S. An assessment of the effects of enzyme inducers on aryl hydrocarbon hydroxylase activity. Res. Commun. Chem. Pathol. Pharmacol. 18:59-66, 1977. 114. Plugge, H. and Safe, S. Vinylchloride metabolism - a review. Chemosphere 6:309-325, 1977. 115. Ecobichon, D.J., Hansell, M.M. and Safe, S. Halogen substituents at the 4- and 4’ positions of biphenyl: influence on hepatic function in the rat. Toxicol. Appl. Pharmacol. 42:359-366, 1977. 116. Chittim, B., Safe, S., Ruzo, L.O., Hutzinger, O. and Zitko, V. Synthesis and spectroscopic and gas chromatographic behavior of isomeric chlorinated terphenyls. Agr. Food Chem. 25:323-326, 1977. 117. Ruzo, L.O., Sundstrom, G., Hutzinger, O. and Safe, S. Heavy-atom effects in the photoreactions of halogenated aromatic compounds. Recueil, Journal of the Royal Netherlands Chemical Society 96:249-251, 1977. 118. Safe, L.M., Safe, S.H., Subden, R.E. and Morris, D.C. Sterol content and polyene antibiotic resistance in isolates of Candida krusei, Candida parakrusei and Candida tropicalis. Can. J. Microb. 23:398-401, 1977. 119. Subden, R.E., Safe, L., Morris, D.C., Brown, R.G. and Safe, S. Eburicol, lichesterol, ergosterol and obtusifoliol from polyene antibiotic-resistant mutants of Candida albican. Can. J. Microb. 23:751-754, 1977. 120. Safe, S., Hutzinger, O., Crocker, J.F.S. and Digout, S.C. Identification of toxic impurities in commercial diphenylamine. Bull. Environ. Contamin. Toxicol. 17:204-207, 1977. 121. Chittim, B., Safe, S., Bunce, N.J., Ruzo, L., Olie, K. and Hutzinger, O. The protolysis of chlorinated p-terphenyls. Can. J. Chem. 56:1253-1260, 1978. 122. Bunce, N.J., Kumar, J., Ravanol., L. and Safe, S. Photochemistry of chlorinated biphenyls in iso- octane solution. J. Chem. Soc., Perkin II:880-884, 1978. 123. Rozee, K.R., Lee, S.H.S., Crocker, J.F.S. and Safe, S. Enhanced virus replication in mammalian cells exposed to commercial emulsifiers. Appl. Environ. Microbiol. 35:297- 300, 1978. 124. Wyndham, C. and Safe, S. The in vitro metabolism of 4-chlorobiphenyl by control and induced rat liver microsomes. Biochemistry 17:208-215, 1978. 125. Kohli, J., Wyndham, C., Smylie, M. and Safe, S. Metabolism of bromobiphenyls. Biochem. Pharmacol. 27:1245-1249, 1978. 126. Sparling, J., Chittim, B., Clegg, B.S., Safe, S.H. and Crocker, J.F.S. The tissue distribution and clearance of Aerotex 3470, an aromatic hydrocarbon solvent.

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Chemosphere 7:607-614, 1978. 127. Crocker, J., Digout, S., Bagnell, P., Lee, S., Rozee, K. and Safe, S.H. Viral interaction with pesticide emulsifiers in vivo. Chemosphere 7:597-606, 1978. 128. Lee, S.H.S., Rozee, K.R., Safe, S.H. and Crocker, J.F.S. The properties of emulsifiers that enhance the replication of viruses in cell culture. Chemosphere 7:573- 590, 1978. 129. Safe, S.H., Kohli, J. and Crawford, A. FireMaster BP-6; fractionation, metabolic and enzyme induction studies. Environ. Health Perspect. 23:147-152, 1978. 130. Wyndham, C. and Safe, S.H. A comparison of the in vitro metabolism of biphenyl and 4- chlorobiphenyl by rat liver microsomes. Can. J. BioChem. 56:993-997, 1978. 131. Rahman, R., Safe, S. and Taylor, A. Sporidesmins. Part 17. Isolation of sporidesmin H and sporidesmin J. J. Chem. Soc., Perkin I:1476-1479, 1979. 132. Shushan, B., Safe, S. and Boyd, R.K. Mass spectrometry of polycyclic aromatic hydrocarbons by linked-scan studies of metastable ions. Anal. Chem. 51:156-158, 1979. 133. Ecobichon, D.J., Hansell, M.M. and Safe, S.H. Isomerically pure bromobiphenyl congeners and hepatic mono-oxygenase activities in the rat: influence of position and degree of bromination. Toxicol. Appl. Pharmacol. 47:341-352, 1979. 134. Crawford, A. and Safe, S.H. 4-Chlorobiphenyl metabolism: the effects of chemical inducers. Gen. Pharmacol. 10:227-231, 1979. 135. Wong, A., Basrur, P. and Safe, S.H. The metabolically mediated DNA damage and subsequent DNA repair by 4-chlorobiphenyl in Chinese hamster ovary cells. Res. Commun. Chem. Pathol. Pharmacol. 24:543-550, 1979. 136. Parkinson, A. and Safe, S.H. The detection of enzyme induction by rat liver microsomes prepared by isoelectric precipitation. J. Pharm. Pharmacol. 31:444-447, 1979. 137. Jones, D.H., Kohli, J. and Safe, S. Avian metabolism of halogenated biphenyls. Xenobiotica 9:733-736, 1979. 138. Tulp, T.M., Safe, S. and Boyd, R.K. Fragmentation pathways in electron impact mass spectra of methoxyhalobiphenyls. Biomed. Mass Spectrom. 7:109-114, 1980. 139. Robertson, L.W., Parkinson, A. and Safe, S.H. Induction of both cytochromes P-450 and P-448 by 2,3’,4,4’,5-pentabromobiphenyl, a component of FireMaster. Biochem. Biophys. Res. Commun. 92:175-182, 1980. 140. Parkinson, A., Safe, S.H. and Cockerline, R. Induction of both 3-methylcholanthrene and phenobarbitone-type microsomal enzyme activity by a single polychlorinated biphenyl isomer. Biochem. Pharmacol. 29:259-262, 1980. 141. Parkinson, A., Copp, L. and Safe, S. 4-Chlorobiphenyl hydroxylase: a monoxygenase preferentially induced by 3-methylcholanthrene. In Proceedings: Microsomes, Drug Oxidation and Chemical Carcinogenesis. Academic Press, New York, Vol. II:977-980, 1980. 142. Parkinson, A., Robertson, L.W. and Safe, S. Hepatic microsomal enzyme induction by 2,2’,3,3’,4,4’- and 2,2’,3’,4,4’,5-hexachlorobiphenyl. Life Sciences 27:2333-2337, 1980. 143. Parkinson, A., Cockerline, L., Robertson, L. and Safe, S. Induction of cytochrome P- 448 and P-450 by PCB isomers and congeners. In Proceedings: Microsomes, Drug Oxidation and Chemical Carcinogenesis. Academic Press, New York, Vol. I:579-582, 1980. 144. Purdy, R. and Safe, S. The in vitro metabolism of 2,2’,4,4’,5,5’-hexabromobiphenyl. J. Environ. Pathol. Toxicol. 4:277-284, 1980. 145. Parkinson, A., Copp, L. and Safe, S. The utility of the microsomal 4-chlorobiphenyl hydroxylase enzyme assay in distinguishing between phenobarbitone- and 3- methylcholanthrene-induced microsomal monooxygenases. Anal. BioChem. 105:65-73, 1980.

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146. Parkinson, A., Cockerline, R. and Safe, S. Polychlorinated biphenyl isomers and congeners as inducers of both 3-methylcholanthrene- and phenobarbitone-type microsomal activity. Chem.-Biol. Interact. 29:277-289, 1980. 147. Sparling, J., Fung, D. and Safe, S. Bromo- and chlorobiphenyl metabolism: gas chromatographic-mass spectrometric identification of urinary metabolites and the effects of structure on their rates of excretion. Biomed. Mass Spectrom. 7:13-19, 1980. 148. Sparling, J. and Safe, S. The effects of ortho-chloro substituents on the retention of PCB isomers in rat, rabbit, Japanese quail, guinea pig and trout. Toxicol. Letters 7:23-28, 1980. 149. Sparling, J. and Safe, S. The effects of the degree of ortho-chloro substitution on the pharmacokinetics of five hexachlorobiphenyls in the rat. Chemosphere 9:129-137, 1980. 150. Parkinson, A., Robertson, L. and Safe, S. Reconstituted human breast milk PCBs as potent inducers of aryl hydrocarbon hydroxylase. Biochem. Biophys. Res. Commun. 96:882-889, 1980. 151. Parkinson, A., Robertson, L., Safe, L. and Safe, S. Polychlorinated biphenyls as inducers of hepatic microsomal enzymes: structure-activity rules. Chem.-Biol. Interact. 30:271-285, 1980. 152. Robertson, L., Parkinson, A. and Safe, S. Induction of drug-metabolizing enzymes by fractionated commercial polybrominated biphenyls PBBs. Toxicol. Appl. Pharmacol. 57:254-262, 1981. 153. Mullin, M., Sawka, G., Safe, L., McCrindle, S. and Safe, S. Synthesis of the octa- and nonachlorobiohenyl isomers and congeners and their quantitation in commercial polychlorinated biphenyls and identification in human breast milk. J. Anal. Toxicol. 5:138-142, 1981. 154. Parkinson, A. and Safe, S. Aryl hydrocarbon hydroxylase induction and its relationship to the toxicity of halogenated aryl hydrocarbons. J. Toxicol. Environ. Chem. Rev. 4:1-46, 1981. 155. Robertson, L.W., Parkinson, A., Bandiera, S. and Safe, S. Potent induction of rat liver microsomal drug-metabolizing enzymes by 2,3,3’,4,4’,5-hexabromobiphenyl, a component of FireMaster. Chem.-Biol. Interact. 35:13-24, 1981. 156. Parkinson, A., Robertson, L.W., Safe, L. and Safe, S. Polychlorinated biphenyls as inducers of hepatic microsomal enzymes: effects of diortho substitution. Chem.-Biol. Interact. 35:1-12, 1981. 157. Wong, A.K.L. and Safe, S. Effects of Aroclor 1254-induced rat liver S-9 fraction on benzo[a]pyrene-mediated DNA damage and benzo[a]pyrene metabolism in cultured human skin fibroblasts. Res. Commun. Chem. Pathol. Pharmacol. 33:129-143,1981. 158. Hutzinger, O., Olie, K., Lustenhouwer, J.W.A., Okey, A.B., Bandiera, S. and Safe, S. Polychlorinated dibenzo-p-dioxins and dibenzofurans: a bioanalytical approach. Chemosphere 10:14-25, 1981. 159. Cockerline, R., Shilling, M. and Safe, S. Polychlorinated naphthalenes as hepatic microsomal enzyme inducers in the immature male rat. Gen. Pharmacol. 12:83-87, 1981. 160. Safe, S., Robertson, L., Safe, L., Parkinson, A., Campbell, M.A., Sawyer, T. and Bandiera, S. Polychlorinated biphenyls (PCBs) as inducers of the hepatic microsomal drug-metabolizing enzymes-effects of structure on activity. Drug Metab. and Drug Interact. III:255-270, 1981. 161. Campbell, M.A., Bandiera, S., Robertson, L., Parkinson, A. and Safe, S. Octachloronapthalene induction of hepatic microsomal aryl hydrocarbon hydroxylase activity in the immature male rat. Toxicology 22:123-132, 1981. 162. Robertson, L.W., Parkinson, A., Chittim, B., Bandiera, S., Sawyer, T.W. and Safe, S. Aryl hydrocarbon hydroxylase (AHH) induction by polybrominated biphenyls (PBBs):

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enhancement by photolysis. Toxicology 22:103-114, 1981. 163. Clegg, S., Safe, S. and Crocker, J.F.S. Identification of a toxic impurity in commericial diphenylamine. J. Environ. Sci. Health B16:125-130, 1981. 164. Parkinson, A. and Safe, S. Cytochrome P-450-mediated metabolism of biphenyl and the 4-halobiphenyls. Biochem. Pharmacol. 31:1849-1856, 1982. 165. Bandiera, S., Safe, S. and Okey, A.B. Binding of polychlorinated biphenyls classified as either phenobarbitone-, 3-methylcholanthrene-, or mixed-type inducers to cytosolic Ah receptor. Chem.-Biol. Interact. 39:259-277, 1982. 166. Safe, S. Halogenated hydrocarbons and aryl hydrocarbons identified in human tissues. Toxicol. Environ. Chem. 5:153-165, 1982. 167. Bandiera, S., Sawyer, T., Campbell, M.A., Robertson, L. and Safe, S. Halogenated biphenyls as AHH inducers: effects of different halogen substituents. Life Sciences 1:517-525, 1982. 168. Parkinson, A., Robertson, L. and Safe, S. The binding of metapyrone to dithionite- reduced cytochrome P-450 from rats pretreated with 13 xenobiotics. Biochem. Pharmacol. 3:3489-3494, 1982. 169. Sawyer, T. and Safe, S. PCB isomers and congeners: induction of aryl hydrocarbon hydroxylase and ethoxyresorufin O-deethylase enzyme activities in rat hepatoma cells. Toxicol. Lett. 13:87-94, 1982. 170. Safe, S., Robertson, L.W., Safe, L., Parkinson, A., Bandiera, S., Sawyer, T. and Campbell, M.A. Halogenated biphenyls: molecular toxicology. Can. J. Physiol. Pharmacol. 60:1057-1064, 1982. 171. Robertson, L.W., Parkinson, A., Campbell, M.A. and Safe, S. Polybrominated biphenyls as aryl hydrocarbon hydroxylase inducers: structure-activity correlations. Chem-Biol. Interact. 42:53-66, 1982. 172. Parkinson, A., Robertson, L., Uhlig, L., Campbell, M.A. and Safe, S. 2,3,4,4’,5- Pentachlorobiphenyl: differential effects on the C57BL/6J and DBA/2J inbred mice. Biochem. Pharmacol. 31:2830-2833, 1982. 173. Campbell, M.A., Bandiera, S., Robertson, L., Parkinson, A. and Safe, S. Hepta-, hexa-, tetra- and dichloronaphthalene congeners as inducers of hepatic microsomal drug- metabolizing enzymes. Toxicol. 26:193-205, 1983. 174. Denomme, M.A., Leece, B., Gyorkos, J., Homonoko, K. and Safe, S. Polychlorinated benzene and phenol congeners as inducers of rat hepatic drug-metabolizing enzymes in immature male Wistar rats. Can. J. Physiol. Pharmacol. 61:1063-1070, 1983. 175. Robertson, L.W., Andres, J., Safe, S.H. and Lovering, S. Toxicity of 3,3′,4,4′ and 2,2′,5,5′-tetrabromobiphenyl: correlation of activity with aryl hydrocarbon hydroxylase induction and lack of protection by antioxidants. J. Toxicol.-Env. Health 11:81-91 1983. 176. Robertson, L.W., Chittim, B., Safe, S., Mullin, M. and Pochini, C. Photodecomposition of a commercial polychlorinated biphenyl (PBB) mixture: high resolution gas chromatographic analysis. J. Agric. Food Chem. 31:454-457, 1983. 177. Parkinson, A., Robertson, L.W. and Safe, S. Induction of rat hepatic microsomal cytochrome P-450 by 2,3’,4,4’,5,5’-hexachlorobiphenyl. Biochem. Pharmacol. 32:2269- 2279, 1983. 178. Parkinson, A., Safe, S., Robertson, L., Thomas, P.E., Ryan, D.E. and Levin, W. Immunochemical quantitation of cytochrome P-450 isozymes and epoxide hydrolase in liver microsomes from polychlorinated and polybrominated biphenyls: a study of structure activity relationships. J. Biol. Chem. 258:5967-5976, 1983. 179. Campbell, M.A., Gyorkos, J., Leece, B., Homonoko, K. and Safe, S. The effects of twenty-two organochlorine pesticides as inducers of the hepatic drug-metabolizing enzymes. Gen. Pharmacol. 14:445-454, 1983. 180. Sawyer, T., Bandiera, S., Safe, S., Hutzinger, O. and Olie, K. Bioanalysis of

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polychlorinated dibenzofuran and dibenzo-p-dioxin mixtures in fly ash. Chemosphere 12:529-535, 1983. 181. Safe, S. 2,3,7,8-TCDD: biochemical effects. Chemosphere 12:447-451, 1983. 182. Parkinson, A., Thomas, P.E., Ryan, D.E., Reik, L.M., Safe, S.H., Robertson, L.W. and Levin, W. Differential time course induction of rat liver microsomal cytochrome P-450 isozymes and epoxide hydrolase by Aroclor 1254. Arch. Biochem. Biophys. 225:203- 215, 1983. 183. Bandiera, S., Sawyer, T.W., Campbell, M.A., Fujita, T. and Safe, S. Competitive binding to the cytosolic 2,3,7,8-TCDD receptor effects of structure on the affinities of substituted halogenated biphenyls: a QSAR analysis. Biochem. Pharmacol. 32:3803-3815, 1983. 184. Andres, J., Lambert, I., Robertson, L., Bandiera, S., Sawyer, T., Lovering, S. and Safe, S. The comparative biologic and toxic potencies of polychlorinated biphenyls and polybrominated biphenyls. Toxicol. Appl. Pharmacol. 70:204-215, 1983. 185. Clark, D.A., Sweeney, G., Safe, S, Hancock, E., Kilburn, D.G. and Gauldie, J. Cellular and genetic basis for the suppression of cytotoxic T cell generation by haloaromatic hydrocarbons. Immunopharmacology 6:143-153, 1983. 186. Denomme, M.A., Bandiera, S., Lambert, I., Copp, L., Safe, L. and Safe, S. Polychlorinated biphenyls as phenobarbitone-type inducers of microsomal enzymes- structure activity-relationships for a series of 2,4-dichloro-substituted congeners. Biochem. Pharmacol. 32:2955-2963, 1983. 187. Safe, S. and Safe, L. Synthesis and characterization of twenty-two purified polychlorinated dibenzofuran congeners. J. Agric. Food Chem. 32:68-71, 1984. 188. Rosanoff, K.A., Jones, D.H. and Sawyer, T.W. A comparison of avian and rodent S-9 liver homogenates in the Ames test. Res. Commun Chem. Pathol. Pharmacol. 44:131- 139, 1984. 189. Mullin, M.D., Pochini, C.M., McCrindle, S., Romkes, M., Safe, S. and Safe, L. High resolution PCB analysis: the synthesis and chromatographic properties of all 209 PCB congeners. Environ. Sci. Toxicol. 18:468-476, 1984. 190. Robertson, L.W., Parkinson, A., Bandiera, S., Lambert, I., Merrill, J. and Safe, S. PCBs and PBBs: biologic and toxic effects on C57BL/6J and DBA/2J mice. Toxicology 31:191-206, 1984. 191. Safe, S. Polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs): biochemistry, toxicology and mechanism of action. C.R.C. Crit. Rev. Toxicol. 13:319- 394, 1984. 192. Fung, D., Safe, S. and Crocker, J.F.S. Detection of trace levels of polyethylene glycol ether surfactants in biological tissues. Environ. Toxicol. Chem. 8:109-118, 1984. 193. Bandiera, S., Farrell, K., Mason, G., Kelley, M., Romkes, M., Bannister, R. and Safe, S. Comparative toxicities of the polychlorinated dibenzofuran (PCDF) and biphenyl (PCB) mixtures which persist in Yusho victims. Chemosphere 13:507-512, 1984. 194. Robertson, L., Safe, S., Parkinson, A., Pellizzari, E., Pochini, C. and Mullin, M.D. The synthesis and identification of highly toxic polybrominated biphenyls in the fire retardant, FireMaster BP-6. J. Agric. Food Chem. 32:1107-1111, 1984. 195. Hayes, M.A., Roberts, E., Roomi, M.W., Safe, S.H., Farber, E. and Cameron, R.G. Comparative influences of different PB-type and 3-MC-type polychlorinated biphenyl - induced phenotypes on cytocidal hepatatoxicity of bromobenzene and acetaminophen. Toxicol. Appl. Pharmacol. 76:118-127, 1984. 196. Bandiera, S., Sawyer, T., Romkes, M., Zmudzka, B., Safe, L., Mason, G., Keys, B. and Safe, S. Polychlorinated dibenzofurans (PCDFs): effects of structure on binding to the 2,3,7,8-TCDD cystolic receptor protein, AHH induction and toxicity. Toxicology 32:131- 144, 1984. 197. Sawyer, T.W., Vatcher, A.D. and Safe, S. Comparative aryl hydrocarbon hydroxylase

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induction activites of commercial PCBs in Wistar rats and rat hepatoma H-4-II E cells in culture. Chemosphere 13:695-701, 1984. 198. Hayes, M.A., Roberts, E., Jago, M.B., Safe, S.H., Farber, E. and Cameron, R.G. Influences of various xenobiotic inducers on cytocidal toxicity of lasiocarpine and senecionine in primary cultures of rat hepatocytes. J. Toxicol. Environ. Health 14:683- 694, 1984. 199. Shepherd, E.C., Phillips, T.D., Irvin, T.R., Safe, S.H. and Robertson, L.W. Aflatoxin B1 metabolism in the rat: polyhalogenated biphenyl enhanced conversion to aflatoxin M1. Xenobiotica 14:741-750, 1984. 200. Safe, S., Bandiera, S., Sawyer, T., Robertson, L., Parkinson, A., Thomas, P.E., Ryan, D., Reik, L.M., Levin, W., Denomme, M.A. and Fujita, T. PCBs: structure-function relationships and mechanism of action. Environ. Health Perspect. 60:47-56, 1985. 201. Fung, D., Safe, S., Boyd, R.K. and Chittim, B.G. GC/MS analysis of specific isomers of polychlorodibenzofurans. Biomed. Mass Spectrom. 12:247-253, 1985. 202. Safe, S., Bandiera, S., Sawyer, T., Zmudzka, B., Mason, G., Romkes, M., Denomme, M.A., Sparling, J., Okey, A.B. and Fujita, T. Effects of structure on binding to the 2,3,7,8-TCDD receptor protein and AHH induction - halogenated biphenyls. Environ. Health Perspect. 61:21-33, 1985. 203. Safe, S., Safe, L. and Mullin, M. Polychlorinated biphenyls (PCBs) - congener-specific analysis of a commercial mixture and a human milk extract. J. Agric. Food Chem. 33:24-29, 1985. 204. Gyorkos, J., Denomme, M.A., Leece, B., Homonoko, K., Valli, V.E. and Safe, S. Reconstituted halogenated hydrocarbon pesticide and pollutant mixtures found in human tissues: effects on the immature male Wistar rat after short term exposure. Can. J. Physiol. Pharmacol. 63:36-43, 1985. 205. Denomme, M.A., Homonoko, K, Fujita, T., Sawyer, T. and Safe, S. Effects of substituents on the cytosolic receptor binding avidities and aryl hydrocarbon hydroxylase induction potencies of 7-substituted-2,3-dichlorodibenzo-p-dioxins - a QSAR analysis. Mol. Pharmacol. 27:656-661, 1985. 206. Haake, J.M., Merrill, J.C. and Safe, S. The in vitro metabolism of benzo[a]pyrene by polychlorinated and polybrominated biphenyl induced rat hepatic microsomal monooxygenases. Can. J. Physiol. Pharmacol. 63:1096-1100, 1985. 207. Kelley, M., Lambert, I., Merrill, J. and Safe, S. 1,4-Bis[2-(3,5- dichloropyridyloxy)]benzene (TCPOBOP) and related compounds as inducers of hepatic monooxygenases: structure-activity effects. Biochem. Pharmacol. 34:3489-3494, 1985. 208. Halverson, M.R., Phillips, T.D., Safe, S.H. and Robertson, L.W. Metabolism of aflatoxin B, by rat hepatic microsomes induced by polyhalogenated biphenyl congeners. Appl. Environ. Microb. 49:882-886, 1985. 209. Merrill, J., Kim, H.L. and Safe, S. Hymenoxon: biologic and toxic effects. BioChem. Pharmacol. 34:3383-3386, 1985. 210. Sawyer, T.W. and Safe, S. In vitro AHH induction by polychlorinated biphenyl and dibenzofuran mixtures: additive effects. Chemosphere 14:79-84, 1985. 211. Hayes, M.A., Safe, S.H., Armstrong, D. and Cameron, R.G. Influence of cell proliferation on initiating activity of pure polychlorinated biphenyls and complex mixtures in resistant hepatocyte in vivo assays for carcinogenicity. J. Natl. Cancer Inst. 74:1037-1041, 1985. 212. Leece, B., Denomme, M.A., Towner, R., Li, S.M.A. and Safe, S. Polychlorinated biphenyls: correlation between in vivo and in vitro quantitative structure-activity relationships (QSARs). J. Toxicol. Environ. Health 16:379-388, 1985. 213. Mason, G., Sawyer, T., Keys, B., Bandiera, S., Romkes, M., Piskorska-Pliszczynska, J., Zmudzka, B. and Safe, S. Polychlorinated dibenzofurans (pcdfs): correlation between

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in vivo and in vitro structure-activity relationships. Toxicology 37:1-12, 1985. 214. Safe, S., Sawyer, T., Mason, G., Bandiera, S., Keys, B., Romkes, M., Piskorska- Plizczcynska, J., Zmudska, B. and Safe, L. Polychlorinated dibenzofurans: quantitative structure-activity relationships. Chemosphere 14:675-683, 1985. 215. Keys, B., Hlavinka, M., Mason, G. and Safe, S. Modulation of rat hepatic microsomal testosterone hydroxylases by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related toxic isostereomers. Can. J. Physiol. Pharmacol. 63:1537-1542, 1985. 216. Hayes, M.A., Roberts, E., Safe, S.H., Farber, E. and Cameron, R.G. Influences of different polychlorinated biphenyls on cytocidal, mitoinhibitory, and nodule-selecting activities of N-2-fluorenvlacetamide in rat liver. J. Natl. Cancer Inst. 76:683-691, 1986. 217. Denomme, M.A., Leece, B., Li, A., Towner, R. and Safe, S. Elevation of 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) polychlorinated biphenyls: structure-activity relationships. BioChem. Pharmacol. 35:277-282, 1986. 218. Safe, S. Comparative toxicology and mechanism of action of polychlorinated dibenzo-p- dioxins and dibenzofurans. Ann. Rev. Pharmacol. Toxicol. 26:371-399, 1986. 219. Donnelly, K.C., Jones, D.H. and Safe, S. The bacterial mutagenicity of nitropolychlorinated dibenzo-p-dioxins. Mut. Res. 169:17-22, 1986. 220. Kennel, S.J., Jason, C., Albro, P.W., Mason, G. and Safe, S.H. Monoclonal antibodies to chlorinated dibenzo-p-dioxins. Toxicol. Appl. Pharmacol. 82:256-263, 1986. 221. Piskorska-Pliszczynska, J., Keys, B., Safe, S. and Newman, M.S. The cytosolic receptor binding affinities and AHH induction potencies of 29 polynuclear aromatic hydrocarbons. Toxicol. Lett. 34:67-74, 1986. 222. Denomme, M.A., Homonko, K., Fujita, T., Sawyer, S. and Safe, S. Substituted polychlorinated dibenzofuran receptor binding affinities and AHH induction potencies - a QSAR analysis. Chem. Biol. Interact. 57:175-187, 1986. 223. Keys, B., Piskorska-Pliszczynska, J. and Safe, S. Polychlorinated dibenzofurans as 2,3,7,8-TCDD antagonists: in vitro inhibition of monooxygenase enzyme induction. Toxicol. Lett. 31:151-158, 1986. 224. Mason, G. and Safe, S. Synthesis, biologic and toxic effects of the major 2,3,7,8- tetrachlorodibenzo-p-dioxin metabolites in the rat. Toxicology 41:153-159, 1986. 225. Mason, G., Farrell, K., Keys, B., Piskorska-Pliszczynska, J., Safe, L. and Safe, S. Polychlorinated dibenzo-p-dioxins: quantitative in vitro and in vivo structure-activity relationships. Toxicology 41:21-31, 1986. 226. Sawyer, T., Jones, D., Rosanoff, K., Mason, G., Piskorska-Pliszczynska, J. and Safe, S. The biologic and toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in chickens. Toxicology 39:197-206, 1986. 227. Scheutz, E.G., Wrighton, S.A., Safe, S.H. and Guzelian, P.S. Regulation of cytochrome P-450p by phenobarbital and phenobarbital-like inducers in adult rat hepatocytes in primary monolayer culture and in vivo. Biochemistry 25:1124-1133, 1986. 228. Leece, B.D., Denomme, M.A., Li, S.M.A., Towner, R.A., Gyorkos, J.W., Chittim, B.G. and Safe, S. Effects of individual terphenyls and polychlorinated terphenyls on rat hepatic microsomal cytochrome P-450-dependent monooxygenases: structure-activity relationships. Arch. Toxicol. 59:186-189, 1986. 229. Haake, J., Kelley, M., Keys, B. and Safe, S. The effects of organochlorine pesticides as inducers of testosterone and benzo[a]pyrene hydroxylases. Gen. Pharmacol. 18:165- 169, 1987. 230. Kamps, C. and Safe, S. Binding of polynuclear aromatic hydrocarbons to the rat 4S cytosolic binding protein: structure-activity relationships. Cancer Lett. 34:129-137, 1987. 231. Romkes, M., Piskorska-Pliszczynska, J. and Safe, S. Effects of 2,3,7,8- tetrachlorodibenzo-p-dioxin on hepatic and uterine estrogen receptor levels in rats.

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Toxicol. Appl. Pharmacol. 87:306-314, 1987. 232. Safe, S. Determination of the 2,3,7,8-TCDD toxic equivalent factors: support for the use of the in vitro AHH induction assay. Chemosphere 16:791-802, 1987. 233. Mason, G., Zacharewski, T., Denomme, M.A., Safe, L. and Safe, S. Polybrominated dibenzo-p-dioxins and related compounds: quantitative in vivo and in vitro structure- activity relationships. Toxicology 44:245-255, 1987. 234. Bannister, R. and Safe, S. Synergistic interactions of 2,3,7,8-TCDD and 2,2′,4,4′,5,5′- hexachlorobiphenyl in C57BL/6J and DBA/2J mice: role of the Ah receptor. Toxicology 44:159-169, 1987. 235. Waddell, D.S., McKinnon, H.S., Chittim, B.G., Safe, S. and Boyd, R.K. Gas chromatographic/mass spectrometric characteristics of purified synthetic isomers of tetrachlorodibenzofuran. Biomed. Mass Spectrom. 14:457-464, 1987. 236. Farrell, K. and Safe, S. Absence of positive cooperativity in the binding of 2,3,7,8- tetrachlorodibenzo-p-dioxin to its cytosolic receptor protein. BioChem. J. 244:539-546, 1987. 237. Haake, J.M., Safe, S., Mayura, K. and Phillips, T.D. Aroclor 1254 as an antagonist of the teratogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol. Letters 38:299-306, 1987. 238. Bannister, R., Davis, D., Zacharewski, T., Tizard, I. and Safe, S. Aroclor 1254 as a 2,3,7,8-tetrachlorodibenzo-p-dioxin antagonist: effects on enzyme induction and immunotoxicity. Toxicology 46:29-42, 1987. 239. Leece, B., Denomme, M.A., Towner, R., Li, S.M.A., Landers, J.A. and Safe, S. Nonadditive interactive effects of polychlorinated biphenyl congeners in rats: role of the 2,3,7,8-tetrachlorodibenzo-p-dioxin receptor. Can. J. Physiol. Pharmacol. 65:1908- 1912, 1987. 240. Kelley, M., Hantelle, P., Safe, S., Levin, W. and Thomas, P.E. Coinduction of cytochrome P-450 isozymes in rat liver by 2,4,5,2′,4′,5′-hexachlorobiphenyl or 3- methoxy-4-aminoazobenzene. Mol. Pharmacol. 32:206-211, 1987. 241. Kim, H.L., Safe, S.H. and Calhoun, M.C. Quantitation of hymenoxon and related sesquiterpene lactones. J. Agric. Food Chem. 35:891-895, 1987. 242. Farrell, K., Safe, L. and Safe, S. Synthesis and Ah receptor binding properties of radiolabeled polychlorinated dibenzofuran congeners. Arch. BioChem. Biophys. 259:185-195, 1987. 243. Romkes, M., Piskorska-Pliszczynska, J., Keys, B., Safe, S. and Fujita, T. Quantitative structure-activity relationships: analysis of interactions of 2,3,7,8-tetrachlorodibenzo-p- dioxin and 2-substituted analogues with rat, mouse, guinea pig and hamster cytosolic receptor. Cancer Res. 47:5108-5111, 1987. 244. Crocker, J.F.S., Safe, S.H. and Acott, P. Effects of chronic phthalate exposure on the kidney. J. Toxicol. Environ. Health 23:433-444, 1988. 245. Merrill, J.C., Kim, H.L., Safe, S., Murray, C.A. and Hayes, M.A. Role of glutathione in the toxicity of the sesquiterpene lactones, hymenoxon and helenalin. J. Toxicol. Environ. Health 23:159-169, 1988. 246. Holcomb, M., Yao, C. and Safe, S. Biologic and toxic effects of polychlorinated dibenzo- p- dioxins and dibenzofurans congeners in the guinea pig: quantitative structure-activity relationships. Biochem. Pharmacol. 37:1535-1539, 1988. 247. Astroff, B., Zacharewski, T., Safe, S., Arlotto, M.P., Parkinson, A., Thomas, P. and Levin, W. 6-Methyl-1,3,8-trichlorodibenzofuran as a 2,3,7,8-tetrachlorodibenzo-p-dioxin antagonist: inhibition of the induction of rat cytochrome P-450 isozymes and related monooxygenase activities. Mol. Pharmacol. 33:231-236, 1988. 248. Romkes, M. and Safe, S. Comparative activities of 2,3,7,8-tetrachlorodibenzo-p-dioxin and progesterone on antiestrogens in the female rat uterus. Toxicol. Appl. Pharmacol.

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92:368-380, 1988. 249. Safe, S.H. The aryl hydrocarbon (Ah) receptor. ISI Atlas of Science. Pharmacology 2:78-83, 1988. 250. Davis, D. and Safe, S. Immunosuppressive activities of polychlorinated dibenzofuran congeners: quantitative structure activity relationships and interactive effects. Toxicol. Appl. Pharmacol. 94:141-149, 1988. 251. Zacharewski, T., Harris, M., Safe, S., Thoma, H. and Hutzinger, O. Applications of the in vitro aryl hydrocarbon hydroxylase induction assay for determining "2,3,7,8-TCDD equivalents": pyrolyzed brominated flame retardants. Toxicology 51:177-189, 1988. 252. Donnelly, K.C., Brown, K.W., Estiri, M., Jones, D.H. and Safe, S. Mutagenic potential of binary mixtures of nitro-polychlorinated dibenzo-p-dioxins and related compounds. J. Toxicol. Environ. Health 24:345-356, 1988. 253. Makary, M., Kim, H.L., Safe, S., Womack, J. and Ivie, G.W. Constitutive and Aroclor 1254- induced hepatic glutathione S-transferase, peroxidase and reductase activities in genetically inbred mice. Comp. Biochem. Physiol. 91:425-429, 1988. 254. Harris, M., Kamps, C. and Safe, S. Role of the 4-5S binding protein in the induction of aryl hydrocarbon hydroxylase in the rat. Carcinogenesis 9:1475-1479, 1988. 255. Astroff, B. and Safe, S. Comparative antiestrogenic activities of 2,3,7,8- tetrachlorodibenzo-p-dioxin and 6-methyl-1,3,8-trichlorodibenzofuran in the female rat. Toxicol. Appl. Pharmacol. 95:435-443, 1988. 256. Piskorska-Pliszczynska, J. and Safe, S. Radioligand-dependent differences in the molecular properties of Ah receptor complexes. Arch. Biochem. Biophys. 267:372-383, 1988. 257. Bunce, N.J., Landers, J.P. and Safe, S. Kinetic models for association 2,3,7,8- tetrachlorodibenzo-p-dioxin with the Ah receptor. Arch. Biochem. Biophys. 267:384- 397, 1988. 258. Randerath, K., Putman, K.L., Randerath, E., Mason, G., Kelley, M. and Safe, S. Organ- specific effects of long term feeding of 2,3,7,8-tetrachlorodibenzo-p-dioxin and 1,2,3,7,8- pentachlorodibenzo-p-dioxin on I-compounds in hepatic and renal DNA of female Sprague-Dawley rats. Carcinogenesis 9:2285-2289, 1988. 259. Parkinson, A, Thomas, P.E., Ryan, D.E., Levin, W., Fujita, T. and Safe, S. Induction of rat liver microsomal cytochrome P-450 isozymes and epoxide hydrolase by a series of 4N-substituted-2,3,4,5-tetrachlorobiphenyls. Toxicology 53:289-300, 1988. 260. Halvorson, M.R., Safe, S.H., Parkinson, A. and Phillips, T.D. Aflatoxin B1 hydroxylation by the pregnenolone-16-carbonitrile-inducible form of rat liver microsomal cytochrome P-450. Carcinogenesis 9:2103-2108, 1988. 261. Safe, S. Polychlorinated biphenyls (PCBs): mutagenicity and carcinogeneity. Mutation Res. 220:31-47, 1989. 262. Haake, J.M. and Safe, S.H. Neonatal phenobarbital imprinting of rat hepatic microsomal testosterone hydroxylations. J. Biochem. Toxicol. 309-319, 1989. 263. Li, S.M.A., Denomme, M.A., Leece, B., Towner, R. and Safe, S. Hexachlorobenzene: biochemical effects and synergistic toxic interactions with 2,3,7,8-tetrachlorodibenzo-p- dioxin. Toxicol. Environ. Chem. 22:215-227, 1989. 264. Harris, M., Zacharewski, T., Astroff, A. and Safe, S. Partial antagonism of 2,3,7,8- tetrachlorodibenzo-p-dioxin-mediated induction of aryl hydrocarbon hydroxylase by a 6- methyl-1,3,8-trichlordibenzofuran: mechanistic studies. Mol. Pharmacol. 35:729-735 1989. 265. Biegel, L., Harris, M., Davis, D., Rosengren, R., Safe, L. and Safe, S. 2,2’,4,4’,5,5’- Hexachlorobiphenyl as a 2,3,7,8-tetrachlorodibenzo-p-dioxin antagonist in C57BL/6J mice. Toxicol. Appl. Pharmacol. 97:561-571, 1989. 266. Zacharewski, T., Safe, L., Safe, S., Chittim, B., DeVault, D., Wilberg, K., Bergqvist, P.A.

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and Rappe, C. Comparative analysis of polychlorinated dibenzo-p-dioxin and dibenzofuran congeners in Great Lakes fish by gas chromatography-mass spectrometry and in vitro enzyme induction activities. Environ. Sci. Technol. 23:730-735, 1989. 267. Bannister, R., Biegel, L., Davis, D., Astroff, B. and Safe, S. 6-Methyl-1,3,8- trichlorodibenzofuran (MCDF) as a 2,3,7,8-tetrachlorodibenzo-p-dioxin antagonist in C57BL/6 mice. Toxicology 54:139-150, 1989. 268. Safe, S., Mason, G., Sawyer, T., Zacharewski, T., Harris, M., Yao, C., Keyes, B., Farrell, K., Holcomb, M., Davis, D., Safe, L., Piskorska-Pliszczynska, J. Leece, B., Denomme, M.A., Hutzinger, O., Thoma, H., Chittim, B. and Madge, J. Development and validation of in vitro induction assays for toxic halogenated mixtures. Toxicol. Ind. Health 5:757- 775, 1989. 269. Landers, J.P., Piskorska-Pliszczynska, J., Zacharewski, T., Bunce, N.J. and Safe, S. Photoaffinity labeling of the nuclear Ah receptor from mouse Hepa 1c1c7 cells using 2,3,7,8-[3H]-tetrachlorodibenzo-p-dioxin. J. Biol. Chem. 264:18463-18471, 1989. 270. Narasimhan, T.R., Kim, H.L. and Safe, S.H. Effects of sesquiterpene lactones on mitochondrial oxidative phosphorylation. Gen. Pharmacol. 20:681-687, 1989. 271. Davis, D. and Safe, S. Dose-response immunotoxicities of commercial polychlorinated biphenyls (PCBs) and their interaction with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol. Letters 48:35-43, 1989. 272. Yao, C. and Safe, S. 2,3,7,8-Tetrachlorodibenzo-p-dioxin-Induced porphyria in genetically inbred mice: partial antagonism and mechanistic studies. Toxicol. Appl. Pharmacol. 100:208-216, 1989. 273. Harris, M., Piskorska-Pliszczynska, J., Zacharewski, T., Romkes, M. and Safe, S. Structure-dependent induction of aryl hydrocarbon hydroxylase in human breast cancer cell lines and characterization of the Ah receptor. Cancer Res. 49:4531-4535, 1989. 274. Zacharewski, T., Harris, M. and Safe, S. Induction of cytochrome P-450-dependent monooxygenase activities in rat hepatoma H-4IIE cells in culture by 2,3,7,8- tetrachlorodibenzo-p-dioxin and related compounds: mechanistic studies using radiolabeled congeners. Arch. Biochem. Biophys. 272:344-355, 1989. 275. Astroff, B. and Safe, S. 6-Substituted-1,3,8-trichlorodibenzofurans as 2,3,7,8- tetrachlorodibenzo-p-dioxin antagonists in the rat: structure-activity relationships. Toxicology 59:285-296, 1989. 276. Makary, M., Kim, H.L., Safe, S., Womack, J. and Ivie, G.W. Induction of glutathione S- transferases in genetically inbred male mice by dietary ethoxyquin hydrochloride. Comp. Biochem. Physiol. 92C:171-174, 1989. 277. Astroff, B. and Safe, S. 2,3,7,8-Tetrachlorodibenzo-p-dioxin as an antiestrogen: effect on rat uterine peroxidase activity. Biochem. Pharmacol. 39:485-488, 1990. 278. Harris, M., Zacharewski, T. and Safe, S. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds on the occupied nuclear estrogen receptor in MCF-7 human breast cancer cell. Cancer Res. 50:3579-3584, 1990. 279. Golas, C.L., Prokipcak, R.D., Okey, A.B., Manchester, D.K., Safe, S. and Fujita, T. Competitive binding of 7-substituted-2,3-dichlorodibenzo-p-dioxin with human placental Ah receptor - a QSAR analysis. Biochem. Pharmacol. 40:737-741, 1990. 280. Randerath, K., Putman, K.L., Randerath, E., Zacharewski, T., Harris, M. and Safe, S. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on I-compounds in hepatic DNA of Sprague-Dawley rats: sex-specific effects and structure-activity relationships. Toxicol. Appl. Pharmacol. 103:271-280, 1990. 281. Merchant, M., Arellano, L. and Safe, S. The mechanism of action of α-naphthoflavone as an inhibitor of 2,3,7,8-tetrachlorodibenzo-p-dioxin induced CYP1A1 gene expression. Arch. Biochem. Biophys. 281:84-89, 1990. 282. Dickerson, R., Howie, L., Davis, D. and Safe, S. The structure-dependent effects of

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hepachlorodibenzofuran isomers in male C57BL/6 mice: immunotoxicity and monooxygenase enzyme induction. Fund. App. Toxicol. 15:298-307, 1990. 283. Davis, D. and Safe, S. Immunosuppressive activities of polychlorinated biphenyls in C57BL/6 mice: structure-activity relationships as Ah receptor agonists and partial antagonists. Toxicology 63:97-111, 1990. 284. Safe, S. Polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and related compounds: environmental and mechanistic considerations which support the development of toxic equivalency factors (TEFs). C.R.C. Crit. Rev. Toxicol 21:51-88, 1990. 285. Howie, L., Dickerson, R., Davis, D. and Safe, S. Immunosuppressive and monooxygenase enzyme induction activities of polychlorinated diphenyl ether congeners in C57BL/6N mice: quantitative structure-activity relationships. Toxicol. Appl. Pharmacol. 105:254-263, 1990. 286. Harris, M., Zacharewski, T., Piskorska-Pliszczynska, J., Rosengren, R. and Safe, S. Structure-dependent induction of aryl hydrocarbon hydroxylase activity in C57BL/6 mice by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related congeners: mechanistic studies. Toxicol. Appl. Pharmacol. 105:243-253, 1990. 287. Astroff, B., Rowlands, C., Dickerson, R. and Safe, S. 2,3,7,8-Tetrachlorodibenzo-p- dioxin inhibition of 17β-estradiol-induced increases in rat uterine EGF receptor binding activity and gene expression. Mol. Cell. Endocrinol. 72:247-252, 1990. 288. Yao, C., Panigrahy, B. and Safe, S. Utilization of cultured chick embryo hepatocytes as in vitro bioassays for polychlorinated biphenyls (PCBs): quantitative structure-induction relationships. Chemosphere 21:1007-1016, 1990. 289. Biegel, L. and Safe, S. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on cell growth and the secretion of the estrogen-induced 34-, 52- and 160-kDa proteins in human breast cancer cells. J. Steroid Biochem. Molec. Biol. 37:725-732, 1990. 290. Donnelly, K.C., Brown, K.W., Anderson, C.S., Barbee, G.C. and Safe, S.H. Metabolism and bacterial mutagenicity of binary mixtures of benzo[a]pyrene and polychlorinated aromatic hydrocarbons. Environ. Mol. Mutagen 16:238-245, 1990. 291. Bunce, N.J., Landers, J.P., Nakai, J.S., Winhall, M.J. and Safe, S. In vitro thermal inactivation of hepatic Ah receptor from several mammalian species. Toxicol. In Vitro 4:87-92, 1990. 292. Kelley, M., Womack, J. and Safe, S. Effects of cytochrome P-450 monooxygenase inducers on mouse hepatic microsomal metabolism of testosterone and alkyoxyresorufins. Biochem. Pharmacol. 39:1991-1998, 1990. 293. Piskorska-Pliszczynska, J., Astroff, B., Zacharewski, T., Harris, M., Rosengren, R., Morrison, V., Safe, L. and Safe, S. Mechanism of action of 2,3,7,8-tetrachlorodibenzo-p- dioxin antagonists: characterization of [125I]-6-methyl-8-iodo-1,3-dichlorodibenzofuran-Ah receptor complexes. Arch Biochem. Biophys. 284:193-200, 1991. 294. Haake-McMillan, J.M. and Safe, S. Neonatal exposure to Aroclor 1254: effects on adult hepatic testosterone hydroxylase activities. Xenobiotica 21:481-489, 1991. 295. Haake-McMillan, J.M. and Safe, S. Neonatal modulation of adult rat hepatic microsomal benzo[a]pyrene hydroxylase activities by Aroclor 1254 or phenobarbital. J. Biochem. Toxicol. 5:203-210, 1991. 296. Nair, R.V., Fisher, E.P., Safe, S., Cortez, C., Harvey, R.G. and DiGiovanni, J. Novel coumarins as potential anticarcinogenic agents. Carcinogenesis 12:65-70, 1991. 297. Zacharewski, T., Harris, M. and Safe, S. Evidence for a possible mechanism of action of the 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated decrease of nuclear estrogen receptor levels in wild-type and mutant Hepa 1c1c7 cells. Biochem. Pharmacol. 41:1931-1939, 1991. 298. Astroff, B., Eldridge, B. and Safe, S. Inhibition of 17β-estradiol-induced and constitutive

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expression of the cellular protooncogene c-fos by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the female rat uterus. Toxicol. Letters 56:305-315, 1991. 299. Wang, X., Narasimhan, T.R., Morrison, V. and Safe, S. In situ and in vitro photoaffinity labeling of the nuclear aryl hydrocarbon (Ah) receptor from transformed rodent and human cell lines. Arch. Biochem. Biophys. 287:186-194, 1991. 300. Davis, D. and Safe, S. Halogenated aryl hydrocarbon-induced suppression of the in vitro plaque-forming cell response to sheep red blood cells is not dependent on the Ah receptor. Immunopharmacology 21:183-190, 1991. 301. Safe, S. Polychlorinated dibenzo-p-dioxins and related compounds: sources, environmental distribution and risk assessment. Environ. Carcin. Ecotox. Reviews C9(2):261-302, 1991. 302. Narasimhan, T.R., Safe, S., Williams, H.J. and Scott, A.I. Effects of 2,3,7,8- tetrachlorodibenzo-p-dioxin on 17-estradiol-induced glucose metabolism in MCF-7 human breast cancer cells: 13C-nuclear magnetic resonance studies. Mol. Pharmacol. 40:1029-1035, 1991. 303. Piskorska-Pliszczynska, J., Morrison, V., Zacharewski, T. and Safe, S. DNA binding properties of the Ah receptor in wild-type and variant mouse hepatoma cells. Arch. Biochem. Biophys. 290:362-368, 1991. 304. Astroff, B. and Safe, S. 6-Alkyl-1,3,8-trichlorodibenzofurans as antiestrogens in female Sprague-Dawley rats. Toxicology 69:187-197, 1991. 305. Safe, S., Astroff, B., Harris, M., Zacharewski, T., Dickerson, R., Romkes, M. and Biegel, L. 2,3,7,8-Tetrachlorodibenzo-p-dioxin and related compounds as antiestrogens: characterization and mechanism of action. Pharmacol. Toxicol. 69, 400-409, 1991. 306. Narasimhan, T.R., Kim, H.L. and Safe, S. Effects of hydroxy polychlorinated biphenyls on mouse liver mitochrondrial oxidation phosphorylation. J. Biochem. Toxicol. 6:229- 236, 1991. 307. Narasimhan, T.R., Mayura, K., Clement, B.A., Safe, S. and Phillips, T.D. Effects of chlorinated phenols on rat embryonic and hepatic mitochondrial oxidative phosphorylation. Environ. Toxicol. Chem. 11:805-814, 1991. 308. Safe, S., Harris, M., Biegel, L. and Zacharewski, T. Mechanism of action of TCDD as an antiestrogen in transformed human breast cancer and rodent cell lines. In Biological Basis for Risk Assessment of Dioxins and Related Compounds, Cold Spring Harbor Laboratory, Banbury, Conference Proceedings #35, pp. 367-377, 1991. 309. Becker, M., Phillips, T. and Safe, S. Polychlorinated diphenyl ethers - a review. Toxicol. Environ. Chem. 33:189-200, 1991. 310. Dickerson, R. and Safe, S. The effects of 6-nitro-1,3,8-trichlorodibenzofuran as a partial estrogen in the female rat. Toxicol. Appl. Pharmacol. 113:55-63, 1992. 311. Merchant, M., Wang, X., Kamps, C., Rosengren, R., Morrison, V. and Safe, S. Mechanism of benzo[a]pyrene-induced CYPIA1 gene expression in mouse Hepa 1c1c7 cells: role of the nuclear 6S and 4S proteins. Arch. Biochem. Biophys. 292:250-257, 1992. 312. Safe, S., Brown, K.W., Donnelly, K.C., Anderson, C.S. and Markiewicz, K. Polychlorinated dibenzo-p-dioxins and dibenzofurans associated with wood-preserving chemical sites: biomonitoring with pine needles. Environ. Sci. Technol. 26:394-397, 1992. 313. Zacharewski, T., Harris, M., Biegel, L., Morrison, V., Merchant, M. and Safe, S. 6- Methyl-1,3,8-trichlorodibenzofuran (MCDF) as an antiestrogen in human and rodent cancer cell lines: evidence for the role of the Ah receptor. Toxicol. Appl. Pharmacol. 113:311-318, 1992. 314. Wang, X., Rosengren, R., Morrison, V. and Safe, S. Characterization of the aryl hydrocarbon receptor in the human C-4II cervical squamous carcinoma cell line.

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Biochem. Pharmacol. 43:1635-1642, 1992. 315. Safe, S. Toxicology, structure-function relationships, human and environmental health impacts of polychlorinated biphenyls (PCBs): progress and problems. Environ. Health Persp. 100:259-268, 1992. 316. Fernandez, P. and Safe, S. Growth inhibitory and antimitogenic activity of 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) in T47D human breast cancer cells. Toxicol. Lett. 61:185-197, 1992. 317. Rosengren, R., Safe, S. and Bunce, N.J. Kinetics of the association of several tritiated polychlorinated dibenzo-p-dioxin and dibenzofuran congeners with hepatic cytosolic Ah receptor from the Wistar rat. Chem. Res. Toxicol. 5:376-382, 1992. 318. Dookwah, H.D., Barhoumi, R., Narasimhan, T.R., Safe, S.H. and Burghardt, R.C. Gap junction in cultured myometrial cells: evidence for a rapid modulation by cAMP. Biol. Reprod. 47:397-407, 1992. 319. Krishnan, V., Narasimhan, T.R. and Safe, S. Development of gel staining techniques for the secretion of procathepsin D (52-kDa) protein in MCF-7 human breast cancer cells. Anal. Biochem. 204:137-142, 1992. 320. Yao, C. and Safe, S. The interaction of 2,3,7,8-tetrachlorodibenzo-p-dioxin and 6- methyl-1,3,8- trichlorodibenzofuran in chick embryo hepatocytes. In Vitro Toxicol. 6:373-380, 1992. 321. Merchant, M., Morrison, V., Santostefano, M. and Safe, S. Mechanism of action of aryl hydrocarbon receptor antagonists: inhibition of 2,3,7,8-tetrachlorodibenzo-p-dioxin- induced CYP1A1 gene expression. Arch. Biochem. Biophys. 298:389-394, 1992. 322. Safe, S. MCDF. Drugs of the Future 17:564-565, 1992. 323. Santostefano, M., Piskorska-Pliszczynska, J., Morrison, V. and Safe, S. Effects of ligand structure on the in vitro transformation of the rat cytosolic aryl hydrocarbon receptor. Arch. Biochem. Biophys. 297:73-79, 1992. 324. Liu, H., Biegel, L., Narasimhan, T.R., Rowlands, C. and Safe, S. Inhibition of insulin-like growth factor-1 responses in MCF-7 cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds. Mol. Cell. Endocrinol. 87:19-28, 1992. 325. Wang, X., Santostefano, M., Lu, Y. and Safe, S. A comparison of the mouse versus human aryl hydrocarbon (Ah) receptor complex: effects of proteolysis. Chem.-Biol. Interact. 85:79-93, 1992. 326. Chaloupka, K., Krishnan, V. and Safe, S. Polynuclear aromatic hydrocarbon carcinogens as antiestrogens in MCF-7 human breast cancer cells. Role of the Ah receptor. Carcinogenesis 13:2223-2239, 1992. 327. Johnson, L., Dickerson, R., Safe, S.H., Nyberg, C.L., Lewis, R.P. and Welsh, Jr., T.H. Reduced Leydig cell volume and function in adult rats exposed to 2,3,7,8- tetrachlorodibenzo-p-dioxin without a significant effects on spermatogenesis. Toxicology 76:103-118, 1992. 328. Ahlborg, U.G., Brouwer, A., Fingerhut, M.A., Jacobson, J.L., Jacobson, S.W., Kennedy, S.W., Kettrup, A.A.F., Koeman, J.H., Poiger, H., Rappe, C., Safe, S.H., Seegal, R.F., Tuomisto, J. and Van den Berg, M. Impact of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls on human and environmental health with special emphasis on application of the toxic equivalence factor concept. Eur. J. Pharmacol. 228:179-199, 1992. 329. Donnelly, K.C., Anderson, C.S., Brown, K.W. and Safe, S.H. Bacterial mutagenicity of soil extracts from a bioremediation facility treating wood-preserving waste. J. Haz. Materials 30:71-81, 1992. 330. Narasimhan, T.R., Mayura, K., Clement, B.A., Safe, S.H. and Phillips, T.D. Effects of chlorinated phenols on rat embryonic and hepatic mitochondrial oxidative phosphorylation. Environ. Toxicol. Chem. 11:805-814, 1992.

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331. Safe, S. Development of bioassays and approaches for the risk assessment of 2,3,7,8- tetrachlorodibenzo-p-dioxin and related compounds. Environ. Health Persp. 101:317- 325, 1993. 332. Mayura, C., Spainhour, C.B., Howie, L., Safe, S. and Phillips, T.D. Teratogenicity and immunotoxicity of 3,3’,4,4’,5-pentachlorobiphenyl in C57BL/6 mice. Toxicology 77:123- 131, 1993. 333. Krishnan, V. and Safe, S. Polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) as antiestrogens in MCF-7 human breast cancer cells: quantitative structure-activity relationships. Toxicol. Appl. Pharmacol. 120:55-61, 1993. 334. Sadhu, D.N., Merchant, M., Safe, S.H. and Ramos, K.S. Modulation of protooncogene expression in rat aortic smooth muscle cells by benzo[a]pyrene. Arch. Biochem. Biophys. 300:124-131, 1993. 335. Arellano, L.O., Wang, X. and Safe, S. Effects of cycloheximide on the induction of CYP1A1 gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in three human breast cancer cell lines. Carcinogenesis 14:219-222, 1993. 336. Santostefano, M., Merchant, M., Arellano, L., Morrison, V., Denison, M.S. and Safe, S. α- Naphthoflavone-induced CYP1A1 gene expression and cytosolic Ah receptor transformation. Mol. Pharmacol. 43:200-206, 1993. 337. Moore, M., Narasimhan, T.R., Wang, X., Krishnan, V., Safe, S., Williams, H.J. and Scott, A.I. Interaction of 2,3,7,8-tetrachlorodibenzo-p-dioxin, 12-O-tetradecanoylphorbol-13- acetate (TPA) and 17β-estradiol in MCF-7 human breast cancer cells. J. Steroid Biochem. Mol. Biol. 44:251-261, 1993. 338. Randerath, E., Randerath, K., Narasimhan, T.R., Wang, X. and Safe, S. Effects of polychlorinated dibenzofurans on I-compounds in hepatic DNA of female Sprague- Dawley rats. Structure dependence and mechanistic considerations. Chem.-Biol. Interact. 88:175-190, 1993. 339. Harper, N., Howie, L., Connor, K., Arellano, L., Craig, A., Dickerson, R. and Safe, S. Immunosuppressive and monooxygenase induction activities of highly chlorinated diphenylether congeners in C57BL/6 and DBA/2 mice. Fund. Appl. Toxicol. 20:496-502, 1993. 340. Harper, N., Connor, K. and Safe, S. Immunotoxic potencies of polychlorinated biphenyl (PCB), dibenzofuran (PCDF) and dibenzo-p-dioxin (PCDD) congeners in C57BL/6 and DBA/2 mice. Toxicology 80:217-227, 1993. 341. Harris, M., Zacharewski, T. and Safe, S. Comparative potencies of Aroclors 1232, 1242, 1248, 1254 and 1260 in male Wistar rats - assessment of the toxic equivalency factor (TEF) approach for polychlorinated biphenyls (PCBs). Fund. Appl. Toxicol. 20:456-463, 1993. 342. Rowlands, C., Krishnan, V., Wang, X., Santostefano, M., Safe, S., Miller, W.R. and Langdon, S. Characterization of the aryl hydrocarbon (Ah) receptor and Ah- responsiveness in human ovarian carcinoma cell lines. Cancer Res. 53:1802-1807, 1993. 343. Merchant, M., Krishnan, V. and Safe, S. Mechanism of action of α-naphthoflavone as an Ah receptor antagonist in MCF-7 human breast cancer cells. Toxicol. Appl. Pharmacol. 120:179-185, 1993. 344. Moore, M., Narasimhan, T.R., Steinberg, M.A., Wang, X. and Safe, S. Potentiation of CYP1A1 gene expression in MCF-7 human breast cancer cells cotreated with 2,3,7,8- tetrachlorodibenzo- p-dioxin and 12-O-tetradecanoylphorbol-13-acetate. Arch. Biochem. Biophys. 305:483-488, 1993. 345. Harper, N., Howie, L., Connor, K., Dickerson, R. and Safe, S. Immunosuppressive effects of highly chlorinated biphenyls and diphenyl ethers on T-cell dependent and

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independent antigens in mice. Toxicology 85:123-135, 1993. 346. Chaloupka, K., Harper, N., Krishnan, V., Santostefano, M., Rodriguez, L.V. and Safe, S. Synergistic activity of aromatic hydrocarbon mixtures as aryl hydrocarbon (Ah) receptor agonists. Chem.-Biol. Interact. 89:141-158, 1993. 347. Liu, H., Santostefano, M., Lu, Y. and Safe, S. 6-Substituted-3,4-benzocoumarins: a new structural class of inducers and inhibitors of CYP1A1-dependent activity. Arch. Biochem. Biophys. 306:223-231, 1993. 348. Lans, M.C., Klasson-Wehler, E., Willemsen, M., Meussen, E., Safe, S. and Brouwer, A. Structure-dependent competitive interaction of hydroxy-polychlorobiphenyls-dibenzo-p- dioxins and -dibenzofurans with human transthyretin. Chem. Biol. Interact. 88:7-21, 1993. 349. Wang, X., Porter, W., Krishnan, V., Narasimhan, T.R. and Safe, S. Mechanism of 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD)-mediated decrease of the nuclear estrogen receptor in MCF-7 human breast cancer cells. Mol. Cell. Endocrinol. 96:159-166, 1993. 350. Safe, S. Polychlorinated biphenyl (PCBs): environmental impact, biochemical and toxic responses and implications for assessment. C.R.C. Crit. Rev. In Toxicol. 24:87-149, 1994. 351. Fernandez, P., Burghardt, R., Smith, R., Nodland, K. and Safe, S. High passage T47D human breast cancer cells: altered endocrine and 2,3,7,8-tetrachlorodibenzo-p-dioxin responsiveness. Eur. J. Pharmacol. 270:53-66, 1994. 352. Moore, M., Wang, X., Lu, Y-F., Wormke, M., Craig, A., Gerlach, J., Burghardt, R. and Safe, S. Benzo[a]pyrene resistant (BaPR) human breast cancer cells: a unique aryl hydrocarbon (Ah)- nonresponsive clone. J. Biol. Chem. 269:11751-11759, 1994. 353. Safe, S. Dietary and environmental estrogens and their possible role in human disease. Environ. Sci. Pollut. Res. 1:29-33, 1994. 354. Narasimhan, T.R., Craig, A., Arellano, L., Harper, N., Menache, M., Birnbaum, L. and Safe, S. Relative sensitivities of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced Cyp1a1 and Cyp1a2 gene expression and immunotoxicity in female B6C3F1 mice. Fund. Appl. Toxicol. 23:598-607, 1994. 355. Weber, T.J., Ou, X., Merchant, M., Safe, S.H. and Ramos, K.S. Biphasic modulation of protein kinase C (PKC) activity by polychlorinated dibenzo-p-dioxins (PCDDs) in serum deprived rat aortic smooth muscle cells. J. Biochem. Toxicol. 9:113-119, 1994. 356. Harper, N., Connor, K., Steinberg, M. and Safe, S. An ELISA specific for antibodies to TNP- LPS detects alterations in serum immunoglobulins and isotype switching in C57BL/6 and DBA/2 mice exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds. Toxicology 92:155-167, 1994. 357. Nakai, J.S., Rosengren, R., Winhall, M.J., Safe, S. and Bunce, N.J. Comparative kinetics study of the binding between 2,3,7,8-tetrachlorodibenzo-p-dioxin and related ligands with the hepatic Ah receptors from several rodent species. J. Biochem. Toxicol. 9:199-209, 1994. 358. Randerath, K., Zhou, G.D., Donnelly, K.C., Safe, S. and Randerath, E. DNA damage by wood- preserving waste extracts in vitro without metabolic activation as assayed by [32P]-postlabeling. Cancer Lett. 83:123-128, 1994. 359. Johnson, L., Wilker, C.E., Safe, S.H., Scott, S., Dean, D.D. and White, P.H. 2,3,7,8- Tetrachlorodibenzo-p-dioxin reduces the number, size and organelle content of Leydig cells in adult rat testes. Toxicology 89:49-65, 1994. 360. Lu, Y-F., Wang, X. and Safe, S. Interaction of 2,3,7,8-tetrachlorodibenzo-p-dioxin and retinoic acid in MCF-7 human breast cancer cell. Toxicol. Appl. Pharmacol. 127:1-8, 1994. 361. Thomsen, J.S., Wang, X., Hines, R.N. and Safe, S. Restoration of Ah responsiveness in MDA- MB-231 human breast cancer cells by transient expression of the estrogen

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receptor. Carcinogenesis 15:933-397 1994. 362. Krishnan, V., Wang, X. and Safe, S. ER/Sp1 complexes mediate estrogen-induced cathepsin D gene expression in MCF-7 human breast cancer cells. J. Biol. Chem. 269:15912-15917, 1994. 363. Holcomb, M. and Safe, S. Inhibition of 7,12-dimethylbenzanthracene-induced rat mammary tumor growth by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Cancer Lett. 82:43-47, 1994. 364. Santostefano, M., Liu, H., Wang, X., Chaloupka, K. and Safe, S. Effect of ligand structure on formation and DNA binding of the transformed rat cytosolic aryl hydrocarbon receptor. Chem. Res. Toxicol. 7:544-550, 1994. 365. Sericano, J.L., Safe, S.H., Wade, T.L. and Brooks, J.M. Toxicological significance on non-, mono- and diortho-substituted polychlorinated biphenyls in oysters from Galveston Bay. Environ. Toxicol. Chem. 13:1797-1803, 1994. 366. Liu, H., Santostefano, M. and Safe, S. 2-Phenyl phenanthridinone and related compounds: aryl hydrocarbon receptor agonists and suicide inactivators of P4501A1. Arch. Biochem. Biophys. 313:206-214, 1994. 367. Harper, N., Wang, X., Liu, H. and Safe, S. Inhibition of estrogen-induced progesterone receptor in MCF-7 human breast cancer cells by aryl hydrocarbon (Ah) receptor agonists. Mol. Cell. Endocrinol. 104:47-55, 1994. 368. Ahlborg, U.G., Becking, G.C., Birnbaum, L.S., Brouwer, A., Derks, H.J.G.M., Feeley, M., Golor, G. Hanberg, A., Larsen, J.C., Liem, A.K.D., Safe, S.H., Schlatter, C., Wærn, F., Younes, M. and Yrjänheikki, E. Toxic equivalency factors for dioxin-like PCBs. Chemosphere 28:1049-1067, 1994. 369. Wang, X. and Safe, S. Development of an in vitro model for investigating the formation of the nuclear Ah receptor complex in mouse Hepa 1c1c7 cells. Arch. Biochem. Biophys. 315:285-292, 1994. 370. Liu, H., Wormke, M., Safe, S.H. and Bjeldanes, L.F. Indolo[3,2-b]carbazole: a dietary- derived factor which exhibits both antiestrogenic and estrogenic activity. J. Natl. Cancer Inst. 86:1758-1765, 1994. 371. Chaloupka, K., Santostefano, M., Goldfarb, I.S., Liu, G., Myers, M.J., Tsyrlov, I.B., Gelboin, H.V., Krishnan, V. and Safe, S. Aryl hydrocarbon (Ah) receptor-independent induction of Cyp1a2 gene expression by acenaphthylene and related compounds. Carcinogenesis 15:2835-2840, 1994. 372. Carvan, III, M.J., Santostefano, M., Safe, S. and Busbee, D. Characteristics of a bottlenose dolphin (Tursiops truncatus) kidney epithelial cell line. Marine Mammal Science 10:52-69, 1994. 373. McDonald, S.J., Kennicutt, M.C., Sericano, J., Wade, T.L., Liu, H. and Safe, S. Correlation between bioassay-derived P4501A1 induction activity and chemical analysis of clam, (Laternula elliptica) extracts from McMurdo Sound, Antartica. Chemosphere 28:2237-2248, 1994. 374. Chaloupka, K., Steinberg, M., Santostefano, M., Rodriguez, L.V., Goldstein, L. and Safe, S. Induction of Cyp1a-1 and Cyp1a-2 gene expression by a reconstituted mixture of polynuclear aromatic hydrocarbons in B6C3F1 mice. Chem.-Biol. Interact. 96:207-221, 1995. 375. Lu, Y-F., Santostefano, M., Cunningham, D.M., Threadgill, M.D. and Safe, S. Identification of 3'-methoxy-4'-nitroflavone as a pure aryl hydrocarbon receptor antagonist and evidence for more than one form of the Ah receptor in MCF-7 human breast cancer cells. Arch. Biochem. Biophys. 316:470-477, 1995. 376. Wilker, C.E., Welsh Jr., T.H., Safe, S.H., Narasimhan, T.R. and Johnson, L. Human chorionic gonadotropin protects Leydig cell function against 2,3,7,8-tetrachlorodibenzo- p-dioxin in adult rats: role of Leydig cell cytoplasmic volume. Toxicology 95:93-102,

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1995. 377. Kennicutt, M.C., McDonald, S.J., Sericano, J.L., Boothe, P., Oliver, J., Safe, S., Presley, B.J., Liu, H., Wolfe, D., Wade, T.L., Crockett, A. and Bockus, D. Human contamination of the marine environment - Arthur Harbor and McMurdo Sound, Antarctica. Environ. Sci. Technol. 29:1279-1287, 1995. 378. Safe, S. Environmental and dietary estrogens and human health - is there a problem. Environ. Health Persp. 103:346-351, 1995. 379. Harper, N., Connor, K., Steinberg, M. and Safe, S. Immunosuppressive activity of polychlorinated biphenyl mixtures and congeners: non-additive (antagonistic) interactions. Fund. Appl. Toxicol. 27:131-139, 1995. 380. Harper, N., Steinberg, M., Thomsen, J. and Safe, S. Halogenated aromatic hydrocarbon-induced suppression of the plaque-forming cell response in B6C3F1 splenocytes cultured with allogenic mouse serum: Ah receptor structure-activity relationships. Toxicology 99:199-206, 1995. 381. Donnelly, K.C., Safe, S.H., Randerath, K. and Randerath, E. Bioassay-based risk assessment of complex mixtures. J. Hazardous Materials 4:341-350, 1995. 382. Safe, S., Rodriguez, L.V. and Goldstein, L.S. Toxic equivalency factor approach for risk assessment of combustion by-products. Toxicol. Environ. Chem. 49:181-191, 1995. 383. Safe, S. Do environmental estrogens play a role in development of breast cancer in women and male reproductive problems? Human Ecol. Risk Assess. 1:17-23, 1995. 384. Safe, S., Washburn, K., Zacharewski, T. and Phillips, T. Synthesis and characterization of hydroxylated polychlorinated biphenyls (PCBs) identified in human serum. Chemosphere 31:3017-3023, 1995. 385. Safe, S. Modulation of gene expression and endocrine response pathways by 2,3,7,8- tetrachlorodibenzo-p-dioxin and related compounds. Pharmacol. Therap. 67:247-281, 1995. 386. Merchant, M. and Safe, S. In vitro inhibition of 2,3,7,8-tetrachlorodibenzo-p-dioxin- induced activity by α-naphthoflavone and 6-methyl-1,3,8-trichlorodibenzofuran using an aryl hydrocarbon (Ah)-responsive construct. Biochem. Pharmacol. 50:663-668, 1995. 387. Willett, K., Steinberg, M., Thomsen, J., Narasimhan, T.R., Safe, S., McDonald, S., Beatty, K. and Kennicutt, M.C. Exposure of killifish to benzo[a]pyrene: comparative metabolism DNA adduct formation and aryl hydrocarbon (Ah) receptor agonist activities. Comp. Biochem. Physiol. 112B:93-103, 1995. 388. Wang, X., Thomsen, J.S., Santostefano, M., Rosengren, R., Safe, S. and Perdew, G.H. Comparative properties of the nuclear Ah receptor complex from several human cell lines. Eur. J. Pharmacol. 293:191-205, 1995. 389. Dickerson, R., Howie-Keller, L. and Safe, S. Alkyl polychlorinated dibenzofurans and related compounds as antiestrogens in the female rat uterus: structure-activity studies. Toxicol. Appl. Pharmacol. 135:287-298, 1995. 390. Ruh, M.F., Zacharewski, T., Connor, K., Howell, J., Chen, I. and Safe, S. Naringenin: a weakly estrogenic bioflavonoid which exhibits antiestrogenic activity. Biochem. Pharmacol. 50:1485-1493, 1995. 391. Connor, K., Safe, S., Jefcoate, C.R. and Larsen, M. Structure-dependent induction of CYP2B by polychlorinated biphenyl congeners in female Sprague-Dawley rats. Biochem. Pharmacol. 50:1913-1920, 1995. 392. Krishnan, V., Porter, W., Santostefano, M., Wang, X. and Safe, S. Molecular mechanism of inhibition of estrogen-induced cathepsin D gene expression by 2,3,7,8- tetrachlorodibenzo-p- dioxin (TCDD) in MCF-7 cells. Mol. Cell. Biol. 15:6710-6719, 1995. 393. Safe, S. and Krishnan, V. Chlorinated hydrocarbons: estrogens and antiestrogens. Toxicol. Lett. 82/83:731-736, 1995.

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394. Wang, W.L., Thomsen, J.S., Porter, W., Moore, M. and Safe, S. Effect of transient expression of the estrogen receptor on constitutive and inducible CYP1A1 in Hs578T human breast cancer cells. Br. J. Cancer 73:316-322, 1996. 395. Connor, K., Howell, J., Chen, I., Liu, H., Berhane, K., Sciarretta, C., Safe, S. and Zacharewski, T. Failure of chloro-s-triazine-derived compounds to induce estrogen receptor-mediated responses in vivo and in vitro. Fund. Appl. Toxicol. 30:93-101, 1996. 396. Bowes III, R.C., Steinberg, M.A., Willett, K.L., Parrish, A.R., Zhao, W., Safe, S.H and Ramos, K.S. Atypical cytochrome P-450 induction profiles in glomerular mesangial cells at the mRNA and enzyme level. Biochem. Pharmacol. 52:587-595, 1996. 397. Moore, M., Ruh, M., Steinberg, M. and Safe, S. Isolation and characterization of variant benzo[a]pyrene-resistant T47D human breast cancer cells. Int. J. Cancer 66:117-123, 1996. 398. Lu, Y.-F., Santostefano, M., Cunningham, B.D.M., Threadgill, M.D. and Safe, S. Substituted flavones as aryl hydrocarbon (Ah) antagonists. Biochem. Pharmacol. 51:1077-1087, 1996. 399. Chen, I., Safe, S. and Gjeldanes, L. Indole-3-carbinol and diindolylmethane as aryl hydrocarbon (Ah) receptor agonists and antagonists in T47D human breast cancer cells. Biochem. Pharmacol. 61:1069-1076, 1996. 400. Santostefano, M. and Safe, S. Characterization of the molecular properties of the transformed and nuclear aryl hydrocarbon (Ah) receptor complexes by proteolytic digestion. Chem.-Biol. Interact. 100:221-240, 1996. 401. Hanneman, W.H., Legare, M.E., Tiffany-Castiglioni, E. and Safe, S. The need for cellular, biochemical and mechanistic studies. Neurotoxicol. Teratol. 18:247-250, 1996 402. Harper, N., Steinberg, M. and Safe, S. Immunotoxicity of a reconstituted polynuclear aromatic hydrocarbon mixture in B6C3F1 mice. Toxicology 109:31-38, 1996. 403. Liu, H. and Safe,S. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on insulin- induced responses in MCF-7 human breast cancer cells. Toxicol. Appl. Pharmacol. 138:242-250, 1996. 404. Randerath, E., Zhou, G.-D., Donnelly, K.C., Safe, S.H. and Randerath, K. DNA damage induced in mouse tissue by organic wood-preserving waste extracts as assayed by 32P- postlabeling. Arch. Toxicol. 70:683-695, 1996. 405. Hanneman, W.H., Legare, M.E., Barhoumi, R., Burghardt, R.C., Safe, S. and Tiffany- Castiglioni, E. Stimulation of calcium uptake in cultured rat hippocampal neurons by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicology 112:19-28, 1996. 406. Lu, Y.-F., Sun, G., Wang, X. and Safe, S. Inhibition of prolactin receptor gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin in MCF-7 human breast cancer cells. Arch. Biochem. Biophys. 332:35-40, 1996. 407. Barhoumi, R., Mouneimne, Y., Phillips, T.D., Safe, S.H. and Burghardt, R.C. Alterations of oxytocin-induced calcium oscillations in clone 9 cells by toxin exposure. Fund. Appl. Toxicol. 33:220-228, 1996. 408. Wilker, C., Johnson, L. and Safe, S. Effects of developmental exposure to indole-3- carbinol or 2,3,7,8-tetrachlorodibenzo-p-dioxin on reproductive potential of male rat offspring. Toxicol. Appl. Pharmacol. 141:68-75, 1996. 409. Porter, W., Wang, F., Wang, W., Duan, R. and Safe, S. Role of estrogen receptor/Sp1 complexes in estrogen-induced heat shock protein 27 ene expression. Mol. Endocrinol. 10:1371-1378, 1996. 410. McDonald, S.J., Willett, K.L., Thomsen, J., Beatty, K.B., Connor, K., Narasimhan, T.R., Erickson, C.M. and Safe, S.H. Sublethal detoxification responses to contaminant exposure associated with offshore production platforms. Can. J. Fish. Aquat. Sci. 53:2606-2617, 1996. 411. Zhao, F., Mayura, K., Harper, N., Safe, S.H. and Phillips, T.D. Inhibition of 3,3',4,4',5-

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pentachlorobiphenyl-induced fetal cleft palate and immunotoxicity in C57BL/6 mice by 2,2',4,4',5,5'-hexachlorobiphenyl. Chemosphere 34:1605-1613, 1997. 412. Zhao, F., Mayura, K., Kocurek, N., Edwards, J.F., Kubena, L.F., Safe, S.H. and Phillips, T.D. Inhibition of 3,3',4,4',5,5'-pentachlorobiphenyl-induced chicken embryotoxicity by 2,2',4,4',5,5'- hexachlorobiphenyl. Fund. Appl. Toxicol. 35:1-8, 1997. 413. Rodriguez, L.V., Dunsford, H.A., Steinberg, M., Chaloupka, K., Zhu, L., Safe, S., Womack, J.E. and Goldstein, L.S. Carcinogenicity of benzo[a]pyrene and manufactured gas plant residues in infant mice. Carcinogenesis 18:127-135, 1997. 414. Moore, M., Mustain, M., Daniel, K., Chen, I., Safe, S., Zacharewski, T., Gillesby, B., Joyeux, A. and Balaguer, P. Antiestrogenic activity of hydroxylated polychlorinated biphenyl congeners identified in human serum. Toxicol. Appl. Pharmacol. 142:160-168, 1997. 415. Ramamoorthy, K., Wang, F., Chen, I., Norris, J.D., McDonnell, D.P., Gaido, K.W., Bocchinfuso, W.P., Korach, K.S. and Safe, S. Potency of combined estrogenic pesticides. Science 275:405-406,1997. 416. Ramamoorthy, K., Wang, F., Chen, I., Norris, J.D., McDonnell, D.P., Gaido, K.W., Bocchinfuso, W.P., Korach, K.S. and Safe, S. Estrogenic activity of a dieldrin/toxaphene mixtures in the mouse uterus, MCF-7 human breast cancer cells and yeast-based estrogen receptor assays: no apparent synergism. Endocrinology 138:1520-1527, 1997. 417. Nodland, K.I., Wormke, M. and Safe, S. Inhibition of estrogen-induced activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the MCF-7 human breast cancer and other cell lines transfected with vitellogenin A2 gene promoter constructs. Arch. Biochem. Biophys. 338:67-72, 1997. 418. Wang, W.L., Porter, W., Burghardt, R. and Safe, S. Mechanism of inhibition of MDA- MB-468 breast cancer cell growth by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Carcinogenesis 18:925-933, 1997. 419. Sun, G. and Safe, S. Antiestrogenic activities of alternate substituted polychlorinated dibenzofurans in MCF-7 human breast cancer cells. Cancer Chemotherapy and Pharmacology 40:239-244, 1997. 420. Willett, K.L., Gardinali, P.R., Serican, J.L., Wade, T.L. and Safe, S. Characterization of the rat H4IIE bioassay for evaluation of environmental samples containing polynuclear aromatic hydrocarbons (PAHs). Arch. Environ. Contam. Toxicol. 32:442-448, 1997. 421. Safe, S. Is there an association between exposure to environmental estrogens and breast cancer? Environ. Health Persp. 105(S3):675-678, 1997. 422. Willett, K.L., McDonald, S.J., Steinberg, M.A., Beatty, K.B., Kennicutt, M.C. and Safe, S. Biomarker sensitivity for polynuclear aromatic hydrocarbon contamination in two marine fish species collected in Galveston Bay. Environ. Toxicol. Chem. 16:1472-1479, 1997. 423. McDougal, A., Wilson, C. and Safe, S. Induction of estradiol 2-hydroxylase activity in MCF-7 human breast cancer cells by pesticides and carcinogens. Environ. Toxicol. Pharmacol., 3:195-199, 1997. 424. Connor, K., Ramamoorthy, K., Moore, M., Mustain, M., Chen, I., Safe, S., Zacharewski, T., Gillesby, B., Joyeux, A. and Belaguer, P. Hydroxylated polychlorinated biphenyls (PCBs) as estrogens and antiestrogens: structure-activity relationships. Toxicol. Appl. Pharmacol. 145:111-123, 1997. 425. Wang, F., Porter, W., Xing, W., Archer, T.K. and Safe, S. Identification of a functional imperfect estrogen-responsive element in the 5’-promoter region of the human cathepsin D gene. Biochemistry 36:7793-7801, 1997. 426. Gillesby, B., Santostefano, M., Porter, W., Safe, S., Wu, Z.F. and Zacharewski, T. Identification of a motif within the 5’ regulatory region of pS2 which is responsible for AP- 1 binding and TCDD- mediated suppression. Biochemistry 36:6080-6089, 1997.

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427. Safe, S., Connor, K., Ramamoorthy, K., Gaido, K. and Maness, S. Human exposure to endocrine-active chemicals - hazard assessment problems. Reg. Pharmacol. Toxicol. 26:52-58, 1997. 428. Wang, W., Smith III, R., Burghardt, R. and Safe, S. 17β-Estradiol-mediated growth inhibition of MDA-MB-468 cells stably transfected with the estrogen receptor: cell cycle effects. Mol. Cell. Endocrinol. 133:49-62, 1997. 429. Wilson, C.L., Thomsen, J., Hoivik, D.J., Wormke, M.T., Stanker, L., Holtzapple, C. and Safe, S.H. Aryl hydrocarbon (Ah)-nonresponsiveness in estrogen receptor-negative MDA-MB-231 cells is associated with expression of a variant Arnt protein. Arch. Biochem. Biophys. 346:65-73, 1997. 430. Porter, W., Saville, B., Hoivik, D. and Safe, S. Functional synergy between the transcription factor Sp1 and the estrogen receptor. Mol. Endocrinol. 11:1569-1580, 1997. 431. McDougal, A., Wilson, C. and Safe, S. Inhibition of 7,12-dimethylbenz[a]anthracene- induced rat mammary tumor growth by aryl hydrocarbon receptor agonists. Cancer Lett. 120:53-63, 1997. 432. Safe, S. Xenoestrogens and breast cancer (Editorial). N. Engl. J. Med. 337:1303-1304, 1997. 433. Hoivik, D., Willett, K., Wilson ,C. and Safe, S. Estrogen does not modulate 2,3,7,8- tetrachlorodibenzo-p-dioxin mediated effects in MCF-7 and Hepa 1c1c7 cells. J. Biol. Chem. 272:30270-30274, 1997. 434. Hoivik, D., Wilson, C., Wang, W., Willett, K., Barhoumi, R., Burghardt, R. and Safe, S. Studies on the relationship between estrogen receptor content, glutathione S-transferase π expression and induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin and drug resistance in human breast cancer cells. Arch. Biochem. Biophys. 348:174-182, 1997. 435. Ramamoorthy, K., Vyhlidal, C., Wang, F., Chen, I-C., Safe, S., McDonnell, D.P., Leonard, L.S. and Gaido, K.W. Additive estrogenic activities of a binary mixture of 2’,4’,6’-trichloro- and 2’,3’,4’,5’-tetrachloro-4-biphenylol. Toxicol. Appl. Pharmacol. 147:93-100, 1997 436. Gray, Jr., L.E., Kelce, W.R., Wiese, T., Tyl, R., Gaido, K., Cook, J., Klinefelter, G., Desaulniers, D., Wilson, E., Zacharewski, T., Waller, C., Foster, P., Laskey, J., Reel, J., Giesy, J., Laws, S., McLachlan, J., Breslin, W., Cooper, R., Di Giulio, R., Johnson, R., Purdy, R., Mihaich, E., Safe, S., Sonnenschein, C., Welshons, W., Miller, R., McMaster, S. and Colborn, T. Endocrine screening methods workshop report: detection of estrogenic and androgenic hormonal and antihormonal activity for chemicals that act via receptor or steroidogenic enzyme mechanisms. Reprod. Toxicol. 11:719-750, 1997. 437. Fielden, M.R., Chen, I., Chittim, B., Safe, S.H. and Zacharewski, T. Examination of the estrogenicity of 2,4,6,2’,6’-pentachloro-4-biphenylol (HO-PCB 104), and a further chlorinated derivative, 2,4,6,2’,4’,6’-hexachlorobiphenyl (PCB 155). Environ. Health Persp. 105:1238-1248, 1997. 438. Randerath, K., Zhou, G.-D., Randerath, E., Safe, S.H. and Donnelly, K.C. Comparative [32P]-postlabeling analysis of exogenous and endogenous DNA adducts in mouse skin exposed to a wood-preserving waste extract, a complex mixture of polycyclic and polychlorinated chemicals. Environ. Mol. Mutagenesis 29:372-378, 1997. 439. Safe, S.H. Development, validation and problems with the TEF approach for risk assessment of dioxins and related compounds. J. Animal Sci. 76:134-141, 1998. 440. Safe, S.H. and Gaido, K. Phytoestrogens and anthropogenic estrogenic compounds. Environ. Toxicol. Chem. 17:119-126, 1998. 441. Safe, S. Limitations of the toxic equivalency factor approach for risk assessment of TCDD and related compounds. Teratogenesis, Carcinogenesis and Mutagenesis 17:285-304, 1998.

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442. Wang, F., Hoivik, D., Pollenz, R. and Safe, S. Functional and physical interactions between the estrogen receptor-Sp1 and the nuclear aryl hydrocarbon receptor complexes. Nucl. Acids Res. 26:3044-3052, 1998. 443. Sun, G., Porter, W. and Safe, S. Estrogen-induced retinoic acid receptor α-1 gene expression: role of estrogen receptor-Sp1 complex. Mol. Endocrinol. 12:882-890, 1998. 444. Hong, S.J., Grover, C.A., Safe, S.H., Tiffany-Castiglioni, E. and Frye, G.D. Halogenated aromatic hydrocarbons suppress CA1 field exictatory postsynaptic potentials in rat hippocampal slices. Toxicol. Appl. Pharmacol. 148:7-13, 1998. 445. Duan, R., Porter, W. and Safe, S. Estrogen-induced c-fos protooncogene expression in MCF-7 human breast cancer cells: role of estrogen receptor Sp1 complex formation. Endocrinology 139:1981-1990, 1998. 446. Willett, K.L., Randerath, K., Zhou, G-D. and Safe, S.H. Inhibition of CYP1A1-dependent activity by the PAH fluoranthene. Biochem. Pharmacol. 55:831-839, 1998. 447. Safe, S. Hazard and risk assessment of chemical mixtures using the toxic equivalency factor (TEF) approach. Environ. Health Persp. 106(S4):1051-1058, 1998. 448. Safe, S. Interactions between hormone and chemicals in breast cancer. Annu. Rev. Pharmacol. Toxicol. 38:121-158, 1998. 449. Fiedler, H., Cooper, K., Bergek, S., Hjelt, M., Rappe, C., Bonner, M., Howell, F., Willett, K. and Safe, S. PCDD, PCDF and PCB in farm-raised catfish from southeast United States. Chemosphere 37:1645-1656, 1998. 450. Castro-Rivera, E. and Safe, S. Estrogen- and antiestrogen-responsiveness of HEC1A endometrial adenocarcinoma cells in culture. J. Ster. Biochem. Mol. Biol. 64:287-295, 1998. 451. McDougal, A. and Safe, S. Induction of 16α-/2-hydroxyestrone metabolite ratios in MCF- 7 cells by pesticides, carcinogens and antiestrogens does not predict mammary carcinogens. Environ. Health Persp. 106:203-206, 1998. 452. Wilson, C.L. and Safe, S. Mechanisms of ligand-induced aryl hydrocarbon receptor- mediated biochemical and toxic responses. Toxicologic Pathol. 26:657-671, 1998. 453. Gupta, M., Miggens, J., Parrish, A., Womack, J., Ramos, K.S., Rodriguez, L.V., Goldstein, L.S., Holtzapple, C., Stanker, L. and Safe, S.H. Ah receptor-independent induction of CYP1A2 gene expression in genetically inbred mice. Environ. Toxicol. Pharmacol. 5:205-213, 1998. 454. Kuiper, G.G.J.M., Lemmen, J.G., Carlsson, B., Corton, J.C., Safe, S.H., Van der Saag, P.T., Van der Burg, B. and Gustafsson, J.A. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor β. Endocrinology 139:4252-4263, 1998. 455. Gould, J.C., Leonard, L.S., Maness, S.C., Wagner, B.L., Conner,K., Zacharewski, T., Safe, S., McDonnell, D.P. and Gaido, K.W. Bisphenol A interacts with the estrogen receptor α in a distinct manner from estradiol. Mol. Cell. Endocrinol. 142:203-214, 1998. 456. Chen, I., McDougal, A., Wang, F. and Safe, S. Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane. Carcinogenesis 19:1631-1639, 1998. 457. Wang, W., Smith, III, R. and Safe, S. Aryl hydrocarbon receptor-mediated antiestrogenicity in MCF-7 cells: modulation of hormone-induced cell cycle enzymes. Arch. Biochem. Biophys. 356:239-248, 1998. 458. Safe, S., Connor, K. and Gaido, K. Methods for xenoestrogen testing. Toxicol. Lett. 102/103:661-666, 1998. 459. Safe, S., Wang, F., Porter, W., Duan, R. and McDougal, A. Ah receptor agonists as endocrine disruptors: antiestrogenic activity and mechanisms. Toxicol. Lett. 102/103:345-359, 1998. 460. Van den Berg, M., Birnbaum,L., Bosveld, A.T.C., Brunström, B., Cook, P., Feeley, M.,

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Giesy, J.P., Hanberg, A., Hasegawa, R., Kennedy, S.W., Kubiak, T., Larsen, J.C., Van Leeuwen, F.X.R., Liem, A.K.D., Nolt, C., Peterson, R.E., Poellinger, L., Safe, S., Schrenk, D., Tillitt, D., Tysklind, M., Younes, M., Wærn, F. and Zacharewski, T. Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife. Environ. Health Persp. 106:775-792, 1998. 461. Gupta, M., McDougal, A. and Safe, S. Estrogenic and antiestrogenic activities of 16α- and 2- hydroxy metabolites of 17β-estradiol in MCF-7 and T47D human breast cancer cells. J. Ster. Biochem. Mol. Biol. 67:413-419, 1998. 462. Fernandez, P., Wilson, C., Hoivik, D. and Safe, S.H. Altered phenotypic characteristics of T47D human breast cancer cells after prolonged growth in estrogen-deficient medium. Cell. Biol. Inter. 22:623-633, 1998. 463. Xie, W., Duan, R. and Safe, S. Estrogen induces adenosine deaminase gene expression in MCF-7 human breast cancer cells: role of estrogen receptor-Sp1 interactions. Endocrinology 140:219-227, 1999. 464. Ramamoorthy, K., Gupta, M.S., Sun, G., McDougal, A. and Safe, S.H. 3,3’,4,4’- Tetrachlorobiphenyl exhibits antiestrogenic and antitumorigenic activity in the rodent uterus and mammary and in human breast cancer cells. Carcinogenesis 20:115-123, 1999. 465. Qin, C., Singh, P. and Safe, S. Transcriptional activation of insulin-like growth factor binding protein 4 by 17β-estradiol in MCF-7 cells: role of estrogen receptor-Sp1 complexes. Endocrinology 140:2501-2508, 1999. 466. Castro-Rivera, E., Wormke, M. and Safe, S. Estrogen and aryl hydrocarbon responsiveness of ECC-1 endometrial cancer cells. Mol. Cell. Endocrinol. 150:11-21, 1999. 467. Nguyen, T.A., Hoivik, D., Lee, J-E. and Safe, S. Interactions of nuclear receptor coactivator/corepressor proteins with the aryl hydrocarbon receptor complex. Arch. Biochem. Biophys. 367:250-257, 1999. 468. Wang, W., Dong, L., Saville, B. and Safe, S. Transcriptional activation of E2F1 gene expression by 17β-estradiol in MCF-7 cells is regulated by NF-Y - Sp1/estrogen receptor interactions. Mol. Endocrinol. 13:1373-1387, 1999. 469. Wang, F., Wang, W. and Safe, S. Regulation of constitutive gene expression through interactions of Sp1 protein with the nuclear aryl hydrocarbon receptor complex. Biochemistry 38:11490-11500, 1999. 470. Duan, R., Porter, W., Samudio, I., Vyhlidal, C., Kladde, M. and Safe, S. Transcriptional activation of c-fos protooncogene by 17β-estradiol: mechanism of aryl hydrocarbon receptor- mediated inhibition. Mol. Endocrinol. 13:1511-1521, 1999. 471. Safe, S., Qin, C. and McDougal, A. Development of selective aryl hydrocarbon receptor modulators (SARMs) for treatment of breast cancer. Expert Opinion on Investigational Drugs 8:1385-1396, 1999. 472. Safe, S., Wargovich, M.J., Lamartinierre, C.A. and Mukhtar, H. Symposium on mechanisms of action of naturally-occurring anticarcinogens. Toxicol. Sci. 5:1-8, 1999. 473. Dong, L.A.., Wang, W.L., Wang, F., Stoner, M., Reed, J.C., Harigai, M., Samudio, I., Kladde, M.P., Vyhlidal, C. and Safe, S. Mechanisms of transcriptional activation of bcl-2 gene expression by 17β-estradiol in breast cancer cells. J. Biol. Chem. 274:32099- 32107, 1999. 474. Letcher, R.J., van Holsteijn, I., Drenth, H.J., Norstrom, R.J., Bergman, A., Safe, S., Pieters, R. and van den Berg, M. Cytotoxicity and aromatase (CYP19) activity modulation by organochlorines in human placental JEG-3 and JAR choriocarcinoma cells. Toxicol. Appl. Pharmacol. 160:10-20, 1999. 475. Gaido, K.W., Leonard, L.S., Maness, S.C., Galluzzo, J.M., McDonnell, D.P., Saville, B. and Safe, S. Differential interaction of the methoxychlor metabolite HPTE with estrogen

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receptors alpha and beta. Endocrinology 140:5746-5753, 1999. 476. Kester, M.H.A., Bulduk, S., Tibboel, D., Meinl, W., Glatt, H., Falany, C.N., Coughtrie, M.W.H., Bergman, A., Safe, S., Kuiper, G.G., Schuur, A.G., Brouwer, A., and Visser, T.J. Potent inhibition of estrogen sulfotransferase by hydroxylated PCB metabolites: a novel pathway explaining the estrogenic activity of PCBs. Endocrinology 141:1897-1900, 2000. 477. McDougal, A., Sethi-Gupta, M., Ramamoorthy, K., Sun, G., and Safe, S. Inhibition of carcinogen-induced rat mammary tumor growth and other estrogen-dependent responses by symmetrical dihalo-substituted analogs of diindolylmethane. Cancer Letts. 151:169-179, 2000. 478. Safe, S. Endocrine disruptors and human health - is there a problem: an update. Environ. Health Persp. 108:487-493, 2000. 479. Safe, S. Toxicology of persistent organic pollutants. Eur. J. Lipid Sci. Technol. 2:52-53, 2000. 480. Saville, B., Wormke, M., Wang, F., Nguyen, T., Enmark, E., Kuiper, G., Gustafsson, J.- A., and Safe, S. Ligand-, cell- and estrogen receptor subtype (α/β)-dependent activation at GC-rich (Sp1) promoter elements. J. Biol. Chem. 275:5379-5387, 2000. 481. Vyhlidal, C., Samudio, I., Kladde, M., and Safe, S. Transcriptional activation of transforming growth factor α by estradiol: requirement for both a GC-rich site and an estrogen response element half-site. J. Mol. Endocrinol. 24:329-338, 2000. 482. Wang, F., Duan, R., Chirgwin, J., and Safe, S. Transcriptional activation of cathepsin D gene expression by growth factors. J. Mol. Endocrinol. 24:193-202, 2000. 483. Wormke, M., Castro-Rivera, E., Chen, I., and Safe, S. Estrogen and aryl hydrocarbon receptor expression and crosstalk in human Ishikawa endometrial cancer cells. J. Ster. Biochem. Mol. Biol. 72:197-207, 2000. 484. Xie, W., Duan, R., Chen, I., Samudio, I., and Safe, S. Transcriptional activation of thymidylate synthase by 17β-estradiol in MCF-7 human breast cancer cells. Endocrinology 141:2439-2449, 2000. 485. Gaido, K.W., Maness, S.C., McDonnell, D.P., Dehal, S.S., Kupfer, D., and Safe, S. Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Mol. Pharmacol. 58:852-858, 2000. 486. Safe, S., Wormke, M., and Samudio, I. Mechanisms of inhibitory aryl hydrocarbon receptor - estrogen receptor crosstalk in human breast cancer cells. J. Mammary Gland Biol. Neoplasia 5:281-292, 2000. 487. Stoner, M., Wang, F., Wormke, M., Nguyen, T., Samudio, I., Vyhlidal, C., Marme, D., Finkenzeller, G., and Safe, S. Inhibition of vascular endothelial growth factor expression in HEC1A endometrial cancer cells through interactions of estrogen receptor α and Sp3 proteins. J. Biol. Chem. 275:22769-22779, 2000. 488. Yoon, K., Pallaroni, L., Ramamoorthy, K., Gaido, K., and Safe, S. Ligand structure- dependent differences in activation of estrogen receptor α in human HepG2 liver and U2 osteogenic cancer cell lines. Mol. Cell. Endocrinol. 162:211-220, 2000. 489. Wormke, M., Stoner, M., Saville, B., and Safe, S. Crosstalk between estrogen receptor α and the aryl hydrocarbon receptor in breast cancer cells involves unidirectional activation of proteosomes. FEBS Lett. 478:109-112, 2000. 490. Lee, J.-E. and Safe, S. 3',4'-Dimethoxyflavone as an aryl hydrocarbon receptor antagonist in human breast cancer cells. Toxicol. Sci. 58:235-242, 2000. 491. Xie, W., Barwick, J.L., Simon, C.M., Pierce, A.M., Safe, S., Blumberg, B., Guzelian, P.S., and Evans, R.M. Reciprocal activation of xenobiotic response genes by nuclear receptors SXR/PXR and CAR. Genes and Development 14:3014-3023, 2000. 492. Barhoumi, R., Mouneimne, Y., Ramos, K.S., Safe, S., Phillips, T.D., Centonze, V.E.,

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Ainley, C., Gupta, M.S., and Burghardt, R.C. Analysis of benzo[a]pyrene partitioning and cytotoxicity in a rat liver cell line. Toxicol. Sci. 53:264-270, 2000. 493. Stewart, D.M., Johnson, G.A., Vyhlidal, C.A., Burghardt, R.C., Safe, S., Yu-Lee, L.-Y., Bazer, F.W., and Spencer, T.E. Interferon τ activates multiple signal transducer and activator of transcription proteins and has complex effects on interferon-responsive gene transcription in ovine endometrial epithelial cells. Endocrinology 142:98-107, 2001. 494. Wang, F., Samudio, I., and Safe, S. Transcriptional activation of cathepsin D gene expression by 17β-estradiol: mechanism of aryl hydrocarbon receptor-mediated inhibition. Mol. Cell. Endocrinol. 172:91-103, 2001. 495. Porter, W., Wang, F., Duan, R., Qin, C., Castro-Rivera, E., Kim, K. and Safe, S. Transcriptional activation of heat shock protein 27 gene expression by 17β-estradiol and modulation by antiestrogens and aryl hydrocarbon receptor agonists: estrogenic activity of ICI 164,384. J. Mol. Endocrinol. 26:31-42, 2001. 496. Chen, I., Hsieh, T., Thomas, T., and Safe, S. Mechanisms of inhibitory aryl hydrocarbon receptor-estrogen receptor crosstalk in MCF-7 breast cancer cells: identification of genes downregulated by AhR agonists using suppression subtractive hybridization. Gene 262:207-214, 2001. 497. Samudio, I., Vyhlidal, C., Wang, F., Stoner, M., Chen, I., Kladde, M., Barhoumi, R., Burghardt, R., and Safe, S. Transcriptional activation of DNA polymerase α gene expression in MCF-7 cells by 17β-estradiol. Endocrinology 142:1000-1008, 2001. 498. Duan, R., Xie, W., Burghardt, R., and Safe, S. Estrogen receptor-mediated activation of the serum response element in MCF-7 cells through MAPK-dependent phosphorylation of Elk-1. J. Biol. Chem. 276:11590-11598, 2001. 499. Qin, C., Wilson, C., Blancher, C., Taylor, M., Safe, S., and Harris, A. Association of ARNT splice variant with estrogen receptor negative breast cancer, poor induction of vascular endothelial growth factor under hypoxia and poor prognosis. Clin. Cancer Res. 7:818-823, 2001. 500. Safe, S. Molecular biology of the Ah receptor and its role in carcinogenesis. Toxicol. Lett. 120:1-7, 2001. 501. McDougal, A., Gupta, M.S., Morrow, D., Ramamoorthy, K., Lee, J.-E., and Safe, S. Methyl-substituted diindolylmethanes as inhibitors of estrogen-induced growth of T47D cells and mammary tumors in rats. Breast Cancer Res. Treat. 66:147-157, 2001. 502. McDougal, A., Wormke, M., Calvin, J., and Safe, S. Tamoxifen-induced antitumorigenic/antiestrogenic action synergized by a selective Ah receptor modulator. Cancer Res. 61:3902-3907, 2001. 503. Xie, W., Duan, R., and Safe, S. Activation of adenosine deaminase in MCF-7 cells through insulin-like growth factor-estrogen receptor α crosstalk. J. Mol. Endocrinol. 26:217-228, 2001. 504. Sanderson, J.T., Slobbe, L., Lansbergen, G.W.A., Safe, S., and Van den Berg, M. 2,3,7,8-Tetrachlorodibenzo-p-dioxin and diindolylmethanes differentially induce cytochrome P450 1A1, 1B1, and 19 in H295R human adrenocortical carcinoma cells. Toxicol. Sci. 61:40-48, 2001. 505. Castro-Rivera, E., Samudio, I., and Safe, S. Estrogen regulation of cyclin D1 gene expression in ZR-75 breast cancer cells involves multiple enhancer elements. J. Biol. Chem. 276:30853-30861, 2001. 506. Waters, K.M., Safe, S., and Gaido, K.W. Differential gene expression in response to methoxychlor and estradiol through ERα, ERβ, and AR in reproductive tissues of female mice. Toxicol. Sci. 63:47-56, 2001. 507. Safe, S., Pallaroni, L., Yoon, K., Gaido, K., Ross, S., Saville, B., and McDonnell, D. Toxicology of environmental estrogens. Reprod. Fertil. Dev. 13:307-315, 2001. 508. Yoon, K., Pallaroni, L., Stoner, M., Gaido, K., and Safe, S. Differential activation of wild-

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type and variant forms of estrogen receptor α by synthetic and natural estrogenic compounds using a promoter containing three tandem estrogen-responsive elements. J. Ster. Biochem. Mol. Biol. 78:25-32, 2001. 509. Safe, S., McDougal, A., Gupta, M.S., and Ramamoorthy, K. Selective Ah receptor modulators (SAhRMs): progress towards development of a new class of inhibitors of breast cancer growth. J. Women's Cancer 3:37-45, 2001. 510. Lee, J.-E. and Safe, S. Inhibition of CYP1A1 expression by resveratrol in breast cancer cells involves a post-transcriptional mechanism. Biochem. Pharmacol. 62:1113-1124, 2001. 511. Wang, F., Samudio, I. and Safe, S. Transcriptional activation of rat creatine kinase B by 17β-estradiol in MCF-7 cells involves an estrogen responsive element and GC-rich sites. J. Cell Biochem. 84:156-172, 2002. 512. Saville, B., Poukka, H., Wormke, M., Jänne, O.A., Palvimo, J.J., Stoner, M., Samudio, I., and Safe, S. Cooperative coactivation of estrogen receptor α in ZR-75 human breast cancer cells by SNURF and TATA-binding protein. J. Biol. Chem. 277:2485-2497, 2002. 513. Mealey, K.L., Barhoumi, R., Burghardt, R.C., Safe, S., and Kochevar, D.T. Doxycycline induces expression of P glycoprotein in MCF-7 breast carcinoma cells. Antimicrob. Agents Chemother. 46:755-761, 2002. 514. Duan, R., Xie, W., Li, X., McDougal, A., and Safe, S. Estrogen regulation of c-fos gene expression through phosphatidylinositol-3-kinase-dependent activation of serum response factor in MCF-7 breast cancer cells. Biochem. Biophys. Res. Commun. 294:384-394, 2002. 515. Qin, C., Nguyen, T., Stewart, J., Samudio, I., Burghardt, R., and Safe, S. Estrogen upregulation of p53 gene expression in MCF-7 breast cancer cells is mediated by calmodulin kinase IV- dependent activation of an NFκB/CTF-1 complex. Mol. Endocrinol. 16:1793-1809, 2002. 516. Barhoumi, R., Mouneimne, Y., Awooda, I., Safe, S., Donnelly, K.C., and Burghardt, R.C. Characterization of calcium oscillations in normal and benzo[a]pyrene-treated Clone 9 cells. Toxicol. Sci. 68:444-450, 2002. 517. Abdelrahim, M., Samudio, I., Smith, R., Burghardt, R., and Safe, S. Small inhibitory RNA duplexes for Sp1 mRNA block basal and estrogen-induced gene expression and cell cycle progression in MCF-7 breast cancer cells. J. Biol. Chem. 277:28815-28822, 2002. 518. Koliopanus, A., Kleeff, J., Xiao, Y., Safe, S., Zimmerman, A., Buchler, M.W. and Friess, H. Increased aryl hydrocarbon receptor expression offers a potential therapeutic target in pancreatic cancer. Oncogene 21:6059-6070, 2002. 519. Safe, S. and McDougal, A. Mechanism of action and development of selective aryl hydrocarbon receptor modulators for treatment of hormone-dependent cancers. Int. J. Oncol. 20:1123-1128, 2002. 520. Stoner, M., Saville, B., Wormke, M., Dean, D., Burghardt, R., and Safe, S. Hypoxia induces proteasome-dependent degradation of estrogen receptor  in ZR-75 breast cancer cells. Mol. Endocrinol. 16:2231-2242, 2002. 521. Vyhlidal, C., Li, X. and Safe, S. Estrogen regulation of transferrin gene expression in MCF-7 human breast cancer cells. J. Mol. Endocrinol. 29:305-317, 2002. 522. Wormke, M., Stoner, M., Saville, B., Walker, K., Abdelrahim, M., Burghardt, R., and Safe, S. The aryl hydrocarbon receptor mediates degradation of the estrogen receptor α through activation of proteasome. Mol. Cel. Biol. 23:1843-1855, 2003. 523. Qin, C., Burghardt, R., Smith, R., Wormke, M., Stewart, J. and Safe, S. Peroxisome proliferator-activated receptor  agonists induce proteasome-dependent degradation of cyclin D1 and estrogen receptor  in MCF-7 breast cancer cells. Cancer Res. 63:958-

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964, 2003. 524. Castro-Rivera, E. and Safe, S. 17-Estradiol- and 4-hydroxytamoxifen-induced transactivation in breast, endometrial and liver cancer cells is dependent on ER-subtype, cell and promoter context. J. Ster. Biochem. Mol. Biol. 84:23-31, 2003. 525. Ngwenya, S. and Safe, S. Cell context-dependent differences in the induction of E2F1 gene expression by 17-estradiol in MCF-7 and ZR-75 cells. Endocrinology 144:1675- 1685, 2003. 526. Khan, S., Abdelrahim, M., Samudio, I. and Safe, S. Estrogen receptor/Sp1 complexes are required for induction of cad gene expression by 17-estradiol in breast cancer cells. Endocrinology 144:2325-2335, 2003. 527. Kim, K., Nguyen, T., Saville, B. and Safe, S. Domains of estrogen receptor α (ERα) required for ER/Sp1-mediated activation of GC-rich promoters by estrogens and antiestrogens in breast cancer cells. Mol. Endocrinol. 17:804-817, 2003. 528. Abdelrahim, M., Smith III, R. and Safe, S. Aryl hydrocarbon receptor gene silencing with small inhibitory RNA differentially modulates Ah-responsiveness in MCF-7 and HepG2 cancer cells. Mol. Pharmacol. 63:1373-1381, 2003. 529. Safe, S. and Wormke, M. Inhibitory aryl hydrocarbon-estrogen receptor α crosstalk and mechanisms of action. Chem. Res. Toxicol. 16:807-816, 2003. 530. Zhang, S., Qin, C. and Safe, S. Flavonoids as aryl hydrocarbon receptor agonists/antagonists effects of structure and cell context. Environ. Health Persp. 111:1877-1882, 2003. 531. Zhang, W., Jiang, J., Qin, C., Thomson, L.M., Parrish, A.R., Safe, S.H. and Simanek, E.E. Triazine dendrimers for drug delivery: evaluation of solubilization properties, activity in cell culture, and in vivo toxicity of a candidate vehicle. Supramolecular Chem. 15:607-616, 2003. 532. Stoner, M., Wormke, M., Saville, B., Samudio, I., Qin, C., Abdelrahim, M. and Safe, S. Estrogen regulation of vascular endothelial growth factor gene expression in ZR-75 breast cancer cells through interaction of estrogen receptor  and Sp proteins. Oncogene 23:1052-1063, 2004. 533. Morrow, D., Qin, C., Smith III, R. and Safe, S. Aryl hydrocarbon receptor-mediated inhibition of LNCaP prostate cancer cell growth and hormone-induced transactivation. J. Ster. Biochem. Mol. Biol. 88:27-36, 2004. 534. Cizmas, L., Zhou, G-D., Safe, S.H., McDonald, T.J., Zhu, L. and Donnelly, K.C. Comparative in vitro and in vivo genotoxicities of 7H-benzo[c]fluorene, manufactured gas plant residue (MGP), and MGP fractions. Environ. Mol. Mutagen. 43:159-168, 2004. 535. Qin, C., Morrow, D., Stewart, J., Spencer, K., Porter, W., Smith III, R., Phillips, T., Abdelrahim, M., Samudio, I. and Safe, S. A new class of peroxisome proliferator- activated receptor  (PPAR) agonists that inhibit growth of breast cancer cells: 1,1- bis(3'-indolyl)-1-(p-substitutedphenyl)methanes. Mol. Cancer Therap. 3:247-259, 2004. 536. Pearce, S.T., Liu, H., Radhakrishnan, I., Abdelrahim, M., Safe, S. and Jordan, V.C. Interaction of the aryl hydrocarbon receptor ligand 6-methyl-1,3,8-trichlorodibenzofuran (MCDF) with estrogen receptor. Cancer Res. 64:2889-2897, 2004. 537. Corbin, C.J., Mapes, S.M., Marcos, J., Shackleton, C.H., Morrow, D., Safe, S., Wise, T., Ford, J.J. and Conley, J. Paralogues of porcine aromatase cytochrome P450: a novel hydroxylase activity and the survival of a duplicated gene. Endocrinology 145:2157- 2164, 2004. 538. Safe, S. and Kim, K. Nuclear receptor-mediated transactivation through interaction with Sp proteins. Progr. Nucleic Acid Res. Mol. Biol. 77:1-36, 2004. 539. Qin, C., Samudio, I., Ngwenya, S. and Safe, S. Estrogen-dependent regulation of ornithine decarboxylase in breast cancer cells through activation of non-genomic cAMP-

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dependent pathways. Mol. Carcin. 40:160-170, 2004. 540. Li, X., Qin, C., Burghardt, R. and Safe, S. Hormonal regulation of lactate dehydrogenase A through activation of protein kinase C pathways in MCF-7 breast cancer cells. Biochem. Biophys. Res. Commun. 320:625-634, 2004. 541. Chintharlapalli, S., Smith III, R., Samudio, I., Zhang, W., and Safe, S. 1,1-Bis(3'-indolyl)- 1-(p-substituted-phenyl)methanes induce peroxisome proliferator-activated receptor γ- mediated growth inhibition, transactivation and differentiation markers in colon cancer cells. Cancer Res. 64:5994-6001, 2004. 542. Abdelrahim, M., Smith III, R., Burghardt, R. and Safe, S. Role of Sp proteins in regulation of vascular endothelial growth factor expression and proliferation of pancreatic cancer cells. Cancer Res. 64:6740-6749, 2004. 543. Hong, J., Samudio, I., Liu, S., Abdelrahim, M. and Safe, S. Peroxisome proliferator- activated receptor γ-dependent activation of p21 in Panc-28 pancreatic cancer cells involves Sp1 and Sp4 proteins. Endocrinology 145:5774-5785, 2004. 544. Fretland, A.J., Safe, S. and Hankinson, H.O. Lack of antagonism of 2,3,7,8- tetrachlorodibenzo-p-dioxin's (TCDD's) induction of cytochrome P4501A1 (CYP1A1) by the putative selective aryl hydrocarbon receptor modulator 6-alkyl-1,3,8- trichlorodibenzofuran (6-MCDF) in the mouse hepatoma cell line Hepa-1c1c7. Chem.- Biol. Inter. 150:161-170, 2004. 545. Chen, C.C., Lee, W.R. and Safe, S. Egr-1 is activated by 17β-estradiol in MCF-7 cells by mitogen-activated protein kinase-dependent phosphorylation of ELK-1. J. Cell Biochem. 93:1063-1074, 2004. 546. Wu, Q., Burghardt, R. and Safe, S. Vitamin D-interacting protein 205 (DRIP205) coactivation of estrogen receptor α (ERα) involves multiple domains of both proteins. J. Biol. Chem. 279:53602-53612, 2004. 547. Purkey, H.E., Palaninathan, S.K., Kent, K.C., Smith, C., Safe, S.H., Sacchettini, J.C. and Kelly, J.W. Hydroxylated polychlorinated biphenyls selectively bind transthyretin in blood and inhibit amyloidogenesis: rationalizing rodent PCB toxicity. Chem. Biol. 11:1719- 1728, 2004. 548. Safe, S. Endocrine disruptors and human health: is there a problem. Toxicology 205:3-10, 2004. 549. Gross-Steinmeyer, K., Stapleton, P.L., Liu, F., Tracy, J.H., Bammler, T.K., Quigley, S.D., Farin, F.M., Buhler, D.R., Safe, S.H., Strom, S.C. and Eaton, D.L. Phytochemical- induced changes in gene expression of carcinogen-metabolizing enzymes in cultured human primary hepatocytes. Xenobiotics 34:619-632, 2004. 550. Lee, J.E., Kim, K., Sacchettini, J.C., Smith, C.V. and Safe, S. Vitamin D-interacting protein 150 (DRIP150) coactivation of estrogen receptor α (ERα) in ZR-75 breast cancer cells is independent of LXXLL motifs. J. Biol. Chem. 280:8819-8830, 2005. 551. Safe, S. Clinical correlates of environmental endocrine disruptors. Trends Endocrinol. Metab. 16:139-144, 2005. 552. Contractor, R., Samudio, I.J., Estrov, Z., Harris, D., McCubrey,J.A., Safe, S.H., Andreeff, M. and Konopleva, M. A novel ring-substituted diindolylmethane 1,1-bis[3'-(5- methoxyindolyl)]-1-(p-t-butylphenyl)methane inhibits ERK activation and induces apoptosis in acute myeloid leukemia. Cancer Res. 65:2890-2898, 2005. 553. Kim, K., Barhoumi, R., Burghardt, R. and Safe, S. Analysis of estrogen receptor α-Sp1 interactions in breast cancer cells by fluorescence resonance energy transfer. Mol. Endocrinol. 19:843-854, 2005. 554. Abdelrahim, M., Lui, S. and Safe, S. Induction of endoplasmic reticulum (ER)-induced stress genes in Panc-1 pancreatic cancer cells is dependent on Sp proteins. J. Biol. Chem. 280:16508-16513, 2005. 555. Chintharlapalli, S., Papineni, S., Konopleva, M., Andreeff, M., Samudio, I. and Safe, S.

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2-Cyano-3,12-dioxo-olean-1,9-dien-28-oic acid (CDDO) and related esters inhibit growth of colon cancer cells through peroxisome proliferator-activated receptor γ-dependent and -independent pathways. Mol. Pharmacol. 68:119-128, 2005. 556. Chintharlapalli, S., Burghardt, R., Papineni, S., Ramaiah, S., Yoon, K. and Safe, S. Activation of Nur77 by selected 1,1-bis(3'-indolyl)-1-(p-substituted phenyl)methanes induces apoptosis through nuclear pathways. J. Biol. Chem. 280:24903-24914, 2005. 557. Abdelrahim, M. and Safe, S.H. Cyclooxygenase-2 inhibitors decrease vascular endothelial growth factor expression in colon cancer cells by enhanced degradation of Sp1 and Sp4 proteins. Mol. Pharmacol. 68:317-329, 2005. 558. Calabro, P., Samudio, I., Safe, S.H., Willerson, J.T. and Yeh, E.T. Inhibition of tumor necrosis factor-α-induced endothelial cell activation by a new class of PPARγ agonists: an in vitro study showing receptor-independent effects.. J. Vascular Res. 42:509-516, 2005. 559. Samudio, I., Konopleva, M., Hail, Jr., N., Shi, Y-X., McQueen, T., Hsu, T., Evans, R., Honda, T., Gribble, G.W., Sporn, M., Gilbert, H.F., Safe, S. and Andreeff, M. 2-Cyano- 3,12-dioxooleana-1,9-diene-28-imidazolide (CDDO-Im) directly targets mitochondrial glutathione to induce apoptosis in pancreatic cancer. J. Biol. Chem. 280:36273-36282, 2005. 560. Safe, S. and Abdelrahim, M. Sp family transcription factors and their role in cancer. Eur. J. Cancer 41:2438-2448, 2005. 561. Chintharlapalli, S., Papineni, S., Baek, S.J., Liu, S. and Safe, S.H. 1,1-Bis(3'indolyl)-1- (p-phenyl substituted)methanes are peroxisome proliferator-activated receptor γ agonists but decrease HCT-116 colon cancer cell survival through receptor-independent activation of early growth response-1 and NAG-1. Mol. Pharmacol. 68:1782-1792, 2005. 562. Mitchell, D.C., Abdelrahim, M., Weng, J., Stafford, L.J., Safe, S., Bar-Eli, M. and Liu, M. Regulation of KiSS-1 metastasis suppressor gene expression in breast cancer cells by direct interaction of transcription factors activator protein-2α and specificity protein-1. J. Biol. Chem. 281:51-58, 2005. 563. Zhang, S., Li, X., Burghardt, R., Smith III, R. and Safe, S. Role of estrogen receptor α (ERα) in insulin-like growth factor-1 (IGF-1)-induced responses in MCF-7 breast cancer cells. J. Mol. Endocrinol. 35:433-447, 2005. 564. Samudio, I., Konopleva, M., Safe, S., McQueen, T. and Andreeff, M. Gluggulsterones induce apoptosis and differentiation in acute myeloid leukemia: identification of isomer- specific antileukemic activities of the pregnadienedione structure. Mol. Cancer Ther. 4:1982-1992, 2005. 565. Lee, S.H., Yamaguchi, K., Kim, J.S., Eling, T.E., Safe, S., Park, Y. and Baek S.J. Conjugated linoleic acid stimulates an anti-tumorigenic protein NAG-1 in an isomer specific manner. Carcinogenesis 27:972-981, 2006. 566. Vanderlaag, K., Samudio, I., Burghardt, R., Barhoumi, R. and Safe,S. Inhibition of breast cancer cell growth and induction of cell death by 1,1-bis(3'-indolyl)methane (DIM) and 5,5'- dibromoDIM. Cancer Lett. 236:198-212, 2006 567. Abdelrahim, M., Newman, K., Vanderlaag, K., Samudio, I. and Safe, S. 3,3'- Diindolylmethane (DIM) and derivatives induce apoptosis in pancreatic cancer cells through endoplasmic reticulum stress-dependent upregulation of DR5. Carcinogenesis 27:717-728, 2006. 568. Fleming, J.G., Spencer, T.E., Safe, S.H. and Bazer, F.W. Estrogen regulates transcription of the ovine oxytocin receptor gene through GC-rich Sp1 promoter elements. Endocrinology 147:899-911, 2006. 569. Mitchell, D.C., Abdelrahim, M., Weng, J., Stafford, L.J., Safe, S., Bar-Eli, M. and Liu, M. Regulation of KiSS-1 metastasis suppressor gene expression in breast cancer cells by

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direct interaction of transcription factors activator protein-2α and specificity protein-1. Biol. Chem. 281:51-58, 2006. 570. Kassouf, W., Chintharlapalli, S., Abdelrahim, M., Nelkin, G., Safe, S. and Kamat, A.M. Inhibition of bladder tumor growth by 1,1-bis(3'-indolyl)-1-(p-substitutedphenyl)methanes: a new class of peroxisome proliferator-activated receptor γ agonists. Cancer Res. 66:412-418, 2006. 571. Li, X., Zhang, S. and Safe, S. Activation of kinase pathways in MCF-7 cells by 17β- estradiol and structurally-diverse estrogenic compounds. J. Ster. Biochem. Mol. Biol. 98:122-132, 2006. 572. Abdelrahim, M., Ariazi, E., Kim, K., Khan, S., Barhoumi, R., Burghardt, R., Liu, S., Hill, D., Finnell, R., Wlodarczyk, B., Jordan, V.C. and Safe, S. 3-Methylcholanthrene and other aryl hydrocarbon receptor agonists directly activate estrogen receptor α. Cancer Res. 66:2459- 2467, 2006. 573. Konopleva, M., Zhang, W., Shi, Y.X., McQueen, T., Tsao, T., Abdelrahim, M., Munsell, M.F., Johansen, M., Yu, D., Madden, T., Safe, S.H., Hung, M.C. and Andreeff, M. Synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid induces growth arrest in HER2- overexpressing breast cancer cells. Mol. Cancer. Ther. 2:317-328, 2006. 574. Higgins, K.J., Abdelrahim, M., Liu, S., Yoon, K. and Safe, S. Regulation of vascular endothelial growth factor receptor-2 expression in pancreatic cancer cells by Sp proteins. Biochem. Biophys. Res. Commun. 345:292-301, 2006. 575. Chintharlapallli, C., Papineni, S. and Safe, S. 1-1-Bis(3'-indolyl)-1-(p-substituted phenyl) methanes inhibit colon cancer cell and tumor growth through PPARγ-dependent and PPARγ- independent pathways. Mol. Cancer Ther. 5:1362-1370, 2006. 576. Ru Lee, W., Chen, C-C., Liu, S. and Safe, S. 17β-Estradiol (E2) induces Cdc25A gene expression in breast cancer cells by genomic and non-genomic pathways. J. Cell. Biochem. 99:209-220, 2006. 577. Barhoumi, R., Awooda, I., Mouneimne, Y., Safe, S. and Burghardt, R. Effects of benzo- a-pyrene on oxytocin-induced Ca2+ oscillations in myometrial cells. Toxicol. Lett. 165:133-141, 2006. 578. Higgins, K.J., Liu, S., Abdelrahim, M., Yoon, K., Vanderlaag, K., Porter, W., Metz, R.P. and Safe, S. Vascular endothelial growth factor receptor-2 expression is induced by 17α-estradiol in ZR-75 breast cancer cells by estrogen receptor α/Sp proteins. Endocrinology 147:3285-3295, 2006. 579. Khan, S., Barhoumi, R., Burghardt, R., Liu, S., Kim K. and Safe, S. Molecular mechanism of inhibitory aryl hydrocarbon receptor-estrogen receptor/Sp1 crosstalk in breast cancer cells. Mol. Endocrinol. 20:2199-2214, 2006. 580. Khan, S., Konstantinov, A., Chittim, B., McAllees, A., Yeo, B. and Safe, S. Structure- dependent Ah receptor agonist activities of chlorinated biphenylenes. Toxicol. In Vitro 20:1234-1237, 2006. 581. Abdelrahim, M., Baker, C.H., Abbruzzese, J.L. and Safe, S. Tolfenamic acid and pancreatic cancer growth, angiogenesis, and Sp protein degradation. J. Natl. Cancer Inst. 98:855-868, 2006. 582. Safe, S. and Papineni, S. The role of xenoestrogenic compounds in the development of breast cancer. Trends Pharmacol. Sci. 27:447-454, 2006. 583. Van den Berg, M., Birnbaum, L.S., Denison, M., De Vito, M., Farland, W., Feeley, M., Fiedler, H., Hakansson, H., Hanberg, A., Haws, L., Rose, M. Safe, S., Schrenk, D., Tohyama, C., Tritscher, A., Tuomisto, J., Tysklind, M., Walker, N. and Peterson, R.E. The 2005 World Health Organization re-evaluation of human and mammalian toxic equivalency factors for dioxins and dioxin-like compounds. Toxicol. Sci. 93:223-241, 2006.

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584. Harding, A.K., Daston, G.P., Boyd, G.R., Lucier, F.W., Safe, S.H., Stewart, J., Tillitt, D.W., Van Der Kraak, G. Endocrine disrupting chemicals research program of the U.S. Environmental Protection Agency: summary of a peer-review report. Environ. Health Perspect. 114:1276-1282, 2006. 585. Liu, S., Abdelrahim, M., Khan, S., Ariazi, E., Jordan, V.C. and Safe, S. Aryl hydrocarbon receptor agonists directly activate estrogen receptor α in MCF-7 breast cancer cells. Biol. Chem. 387:1209-1213, 2006. 586. Lei, P., Abdelrahim, M. and Safe, S. 1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes inhibit ovarian cancer cell growth through peroxisome proliferator- activated receptor-dependent and independent pathways. Mol. Cancer Ther. 5:2324- 2336, 2006. 587. Chintharlapalli, S., Papineni, S. and Safe, S.H. 1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes inhibit growth, induce apoptosis, and decrease the androgen receptor in LNCaP prostate cancer cells through PPARγ-independent pathways. Mol. Pharmacol. 71:558-569, 2007. 588. Cho, S.D., Yoon, K., Chintharlapalli, S., Abdelrahim, M., Pei, P., Hamilton, S., Khan, S., Ramaiah, S.K. and Safe, S. Nur77 agonists induce proapoptotic genes and responses in colon cancer cells through nuclear receptor-dependent and independent pathways. Cancer Res. 67:674-683, 2007. 589. Wu, F. and Safe, S. Differential activation of wild-type estrogen receptor α and C- terminal deletion mutants by estrogens, antiestrogens and xenoestrogens in breast cancer cells. J. Steroid Biochem. Mol. Biol. 103:1-9, 2007. 590. Chintharlapalli, S., Papineni, S., Ramaiah, S.K. and Safe, S. Betulinic acid inhibits prostate cancer growth through inhibition of specificity protein transcription factors. Cancer Res. 67:2816-2823, 2007. 591. Abdelrahim, M., Baker, C.H., Abbruzzese, J.L., Sheikh-Hamad, D., Liu, S., Cho, S.D., Yoon, K. and Safe, S. Regulation of vascular endothelial growth factor receptor-1 (VEGFR1) expression by specificity proteins 1, 3 and 4 in pancreatic cancer cells. Cancer Res. 67:3286-3294, 2007. 592. Lee, J. and Safe, S. Coactivation of estrogen receptor α (ERα)/Sp1 by vitamin D receptor interacting protein 150 (DRIP150). Arch. Biochem. Biophys. 461:200-210, 2007. PMC1978170 593. Chintharlapalli, S., Papineni, S., Jutooru, I., McAlees, A. and Safe, S. Structure- dependent activity of glycyrrhetinic acid derivatives as peroxisome proliferator-activated receptor γ agonists in colon cancer cells. Mol. Cancer Ther. 6:1588-1598, 2007. 594. Reddivari, L., Vanamala, J., Chintharlapalli, S., Safe, S.H. and Miller, J.C. Jr. Anthocyanin fraction from potato extracts is cytotoxic to prostate cancer cells through activation of caspase- dependent and caspase-independent pathways. Carcinogenesis 28:2227-2235, 2007. 595. Khan, S., Liu, S., Stoner, M. and Safe, S. Cobaltous chloride and hypoxia inhibit aryl hydrocarbon receptor-mediated responses in breast cancer cells. Toxicol. Appl. Pharmacol. 223:28-38, 2007. 596. Chintharlapalli, S., Papineni, S., Liu, S., Jutooru, I., Chadalapaka, G., Cho, S.D., Murthy, R.S., You, Y. and Safe, S. 2-Cyano-lup-1-en-3-oxo-20-oic acid, a cyano derivative of betulinic acid, activates peroxisome proliferator-activated receptor γ in colon and pancreatic cancer cells. Carcinogenesis 28:2337-2346, 2007. 597. Su, Y., Vanderlaag, K., Ireland, C., Ortiz, J., Grage, H., Safe, S. and Frankel, A. 1,1- Bis(3'-indolyl)-1-(p-biphenyl)methane inhibits basal-like breast cancer growth in athymic nude mice. Breast Cancer Res. 39:289-304, 2007. 598. Khan, S., Wu, F., Liu, S., Wu, Q. and Safe, S. Role of specificity protein transcription factors in estrogen-induced gene expression in MCF-7 breast cancer cells. J. Mol.

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Endocrinol. 39:289-304, 2007. 599. Mertens-Talcott, S.U., Chintharlapalli, S., Li, X. and Safe, S. The oncogenic microRNA- 27a targets genes that regulate specificity protein transcription factors and the G2-M checkpoint in MDA-MB-231 breast cancer cells. Cancer Res. 67:11001-11011, 2007. 600. York, M., Abdelrahim, M., Chintharlapalli, S., Lucero, S.D. and Safe, S. 1,1'-Bis(3'- indolyl)-1-(p- substituted phenyl)methanes induce apoptosis and inhibit renal cell carcinoma growth. Clin. Cancer Res. 13:6743-6752, 2007. 601. Vanderlaag, K., Su, Y., Frankel, A.E, Grage, H., Smith, R. 3rd, Khan, S. and Safe, S. 1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes inhibit proliferation of estrogen receptor-negative breast cancer cells by activation of multiple pathways. Breast Cancer Res. Treat. 109:273-283, 2007. 602. Papineni, S., Chintharlapalli, S. and Safe, S. Methyl 2-cyano-3,11-dioxo-18β-olean-1,12- dien-30-oate is a peroxisome proliferator-activated receptor γ agonist that induces receptor-independent apoptosis in LNCaP prostate cancer cells. Mol. Pharmacol. 73:553-565, 2008. 603. Tjalkens, R.B., Liu, X., Mohl, B., Wright, T., Moreno, J.A., Carbone, D.L. and Safe, S. The peroxisome proliferator-activated receptor-γ agonist 1,1-bis(3'-indolyl)-1-(p- trifluoromethylphenyl)methane suppresses manganese-induced production of nitric oxide in astrocytes and inhibits apoptosis in co-cultured PC12 cells. J. Neurosci. Res. 81:618-629, 2008. 604. Cho, S.D., Lei, P., Abdelrahim, M., Yoon, K., Liu, S., Guo, J., Papineni, S., Chintharlapalli, S. and Safe, S. 1,1-Bis(3'-indolyl)-1-(p-methoxyphenyl)methane activates Nur77-independent proapoptotic responses in colon cancer cells. Mol. Carcinog. 47:252-263, 2008. 605. Higgins, K.J., Liu, S., Abdelrahim, M., Vanderlaag, K., Liu, X., Porter, W., Metz, R. and Safe, S. Vascular endothelial growth factor receptor-2 expression is downregulated by 17β-estradiol in MCF-7 breast cancer cells by estrogen receptor α/Sp proteins. Mol. Endocrinol. 22:388-402, 2008. 606. Zhang, S., Rowlands, C. and Safe, S. Ligand-dependent interactions of the Ah receptor with coactivators in a mammalian two-hybrid assay. Toxicol. Appl. Pharmacol. 227:196- 206, 2008. 607. Chadalapaka, G., Jutooru, I., McAlees, A., Stefanac, T. and Safe, S. Structure- dependent inhibition of bladder and pancreatic cancer cell growth by 2-substituted glycyrrhetinic and ursolic acid derivatives. Bioorg. Med. Chem. Lett. 18:2633-2639, 2008. 608. Hong, J., Samudio, I., Chintharlapalli, S. and Safe, S. 1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes decrease mitochondrial membrane potential and induce apoptosis in endometrial and other cancer cell lines. Mol. Carcinog. 47:492-507, 2008. 609. Wu, F., Khan, S., Wu, Q., Barhoumi, R., Burghardt, R. and Safe, S. Ligand structure- dependent activation of estrogen receptor α/Sp by estrogens and xenoestrogens. J. Ster. Biochem. Mol. Biol. 110:104-115, 2008. 610. Pacheco-Palencia, L.A., Talcott, S.T., Safe, S. and Mertens-Talcott, S. Absorption and biological activity of phytochemical-rich extracts from açai (Euterpe oleracea Mart.) pulp and oil in vitro. J. Agric. Food Chem. 46:3593-3600, 2008. 611. Chadalapaka, G., Jutooru, I., Chintharlapalli, S., Papineni, S., Smith III, R., Li, X. and Safe, S. Curcumin decreases specificity protein (Sp) expression in bladder cancer cells. Cancer Res. 68:5345-5354, 2008. 612. Lei, P., Abdelrahim, M., Cho S.D., Liu, S., Chintharlapalli, S. and Safe, S. 1,1-Bis(3'- indolyl)-1-(p-substituted phenyl)methanes inhibit colon cancer cell and tumor growth through activation of c-Jun N-terminal kinase. Carcinogenesis 29:1139-1147, 2008. 613. Safe, S., Papineni, S. and Chintharlapalli, S. Cancer chemotherapy with indole-3-

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carbinol, bis(3'-indolyl)methane and synthetic analogs. Cancer Lett. 269:326-338, 2008. 614. Cho, S.D., Chintharlapalli, S., Abdelrahim, M., Papineni, S., Liu, S., Guo, J., Lei, P., Abudayyeh, A. and Safe, S. 5,5'-Dibromo-bis(3'-indolyl)methane induces Krüppel-like factor 4 and p21 in colon cancer cells. Mol. Cancer Ther. 7:2109-2120, 2008. 615. Wu, F., Xu, R., Kim, K., Martin, J. and Safe, S. In vivo profiling of estrogen receptor/specificity protein-dependent transactivation. Endocrinology 149:5696-5705, 2008. 616. Lei, P., Abdelrahim, M., Cho, S.D. and Safe, S. Structure-dependent activation of endoplasmic reticulum stress-mediated apoptosis in pancreatic cancer by 1,1-bis(3'- indolyl)-1-(p-substituted phenyl)methanes. Mol. Cancer Therap. 7:3363-3372, 2008. 617. Lee, S.H., Bahn, J.H., Choi, C.K., Whitlock, N.C., English, A.E., Safe, S. and Baek, S.J. ESE-1/EGR-1 pathway plays a role in tolfenamic acid-induced apoptosis in colorectal cancer cells. Mol. Cancer Therap. 7:3739-3750, 2008. 618. Safe, S. and Kim, K. Nonclassical genomic ER/Sp and ER/Ap-1 signaling pathways. J. Mol. Endocrinol. 41:263-275, 2008. 619. Inamoto, T., Papineni, S., Chintharlapalli, S., Cho, S.D., Safe, S. and Kamat, A.M. 1,1- Bis(3'-indolyl)-1-(p-chlorophenyl)methane activates the orphan nuclear receptor Nurr1 and inhibits bladder cancer growth. Mol. Cancer Ther. 7:3825-3833, 2008. 620. Carbone, D.L., Popichak, K.A., Moreno, J.A., Safe, S. and Tjalkens, R.B. Suppression of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced nitric oxide synthase 2 expression in astrocytes by a novel diindolylmethane analog protects striatal neurons against apoptosis. Mol. Pharmacol. 75:35-43, 2009. 621. Wu, F., Ivanov, I., Xu, R. and Safe, S. Role of Sp transcription factors in hormone- dependent modulation of genes in MCF-7 breast cancer cells: microarray and RNA interference studies. J. Mol. Endocrinol. 42:19-33, 2009. 622. Ichite, N., Chougule, M.B., Jackson, T., Fulzele, S.V., Safe, S. and Singh, M. Enhancement of docetaxel anti-cancer activity by a novel diindolylmethane (DIM) compound in human non-small cell lung cancer. Clin. Cancer Res. 15:543-552, 2009. 623. Fritz, W.A., Lin, T.M., Safe, S., Moore, R.W. and Peterson, R.E. The selective aryl hydrocarbon receptor modulator 6-methyl-1,3,8-trichlorodibenzofuran inhibits prostate tumor metastasis in TRAMP mice. Biochem. Pharmacol. 77:1151-1160, 2009. 624. Barhoumi, R., Catania, J.M., Parrish, A.R., Awooda, I., Tiffany-Castiglioni, E., Safe, S. and Burghardt, R.C. Multiphoton spectral analysis of benzo[a]pyrene uptake and metabolism in breast epithelial cell lines. J. Toxicol. Sci. 34:13-25, 2009. 625. Konduri, S., Colon, J., Baker, C.H., Safe, S., Abbruzzese, J.L., Abudayyeh, A., Basha, M.R. and Abdelrahim, M. Tolfenamic acid enhances pancreatic cancer cell and tumor response to radiation therapy by inhibiting survivin protein expression. Mol. Cancer Ther. 8:533-542, 2009. 626. Jutooru, I., Chadalapaka, G., Chintharlapalli, S., Papineni, S. and Safe, S. Induction of apoptosis and nonsteroidal anti-inflammatory drug-activated gene 1 in pancreatic cancer cells by a glycyrrhetinic acid derivative. Mol. Carcinog. 48:692-702, 2009. 627. Papineni, S., Chintharlapalli, S., Abdelrahim, M., Lee, S.O., Burghardt, R., Abudayyeh, A., Baker, C., Herrera, L. and Safe, S. Tolfenamic acid inhibits esophageal cancer through repression of specificity proteins and c-Met. Carcinogenesis 30:1193-1201, 2009. 628. Zhang, S., Lei, P., Liu, X., Li, X., Walker, K., Kotha, L., Rowlands, C. and Safe, S. The aryl hydrocarbon receptor as a target for estrogen receptor-negative breast cancer chemotherapy. Endocr. Relat. Cancer 16:835-844, 2009. 629. Chintharlapalli, S., Papineni, S., Abdelrahim, M., Abudayyeh, A., Jutooru, I., Chadalapaka, G., Wu, F., Mertens-Talcott, S., Vanderlaag, K., Cho, S.D., Smith, R. 3rd and Safe, S. Oncogenic microRNA-27a is a target for anticancer agent methyl 2-cyano-

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3,11-dioxo-18β-olean-1,12-dien-30-oate in colon cancer cells. Int. J. Cancer 125:1965- 1974, 2009. 630. Lee, S.O., Chintharlapalli, S., Liu, S., Papineni, S., Cho, S.D., Yoon, K. and Safe, S. p21 expression is induced by activation of nuclear nerve growth factor-induced Bα (Nur77) in pancreatic cancer cells. Mol. Cancer Res. 7:1169-1178, 2009. 631. Sreevalsan, S., Jutooru, I., Chadalapaka, G., Walker, M. and Safe, S. 1,1-Bis(3'-indolyl)- 1-(p-bromophenyl)methane and related compounds repress survivin and decrease γ- radiation-induced survivin in colon and pancreatic cancer cells. Int. J. Oncol. 35:1191- 1199, 2009. 632. Da Costa, C.A., Sunyach, C., Giaime, E., West, A., Corti, O., Brice, A., Safe, S., Abou- Sleiman, P.M., Wood, N.W., Takahashi, H., Goldberg, M.S., Shen, J. and Checler, F. Transcriptional repression of p53 by parkin and impairment by mutations associated with autosomal recessive juvenile Parkinson's disease. Nat. Cell Biol. 11:1370-1375, 2009. 633. Liu, X., Abdelrahim, M., Abudayyeh, A., Lei, P. and Safe, S. The nonsteroidal anti- inflammatory drug tolfenamic acid inhibits BT474 and SCBR3 breast cancer cell and tumor growth by repressing erbB2 expression. Mol. Cancer Therap. 8:1207-1217, 2009. 634. Guo, J., Chintharlapalli, S., Lee, S., Cho, S.D., Lei, P., Papineni, S. and Safe, S. Peroxisome proliferator-activated receptor γ-dependent activity of indole ring-substituted 1,1-bis(3'-indolyl)-1-(p-biphenyl)methanes in cancer cells. Cancer Chemother. Pharmacol. 66:141-150, 2010. 635. Choi, K.H., Kim, H.K., Kim, H.J., Choi, E.S., Shin, J.A., Lee, S.O., Chintharlapalli, S., Safe, S., Abdelrahim, M., Kong, G., Choi, H.S., Jung, J.Y., Cho, H.T., Cho, N.P. and Cho, S.D. The p38MAPK pathway is critical for 5,5'-dibromodiindolylmethane-induced apoptosis to prevent oral squamous carcinoma cells. Eur. J. Cancer Prev. 19:153-159, 2010. 636. Cho, S.D., Lee, S.O., Chintharlapalli, S., Abdelrahim, M., Khan, S., Yoon, K., Kamat, A. and Safe, S. Activation of nerve growth factor-induced Bα by methylene-substituted diindolylmethanes in bladder cancer cells induces apoptosis and inhibits tumor growth. Mol. Pharmacol. 77:396-404, 2010. 637. Bredfeldt, T.G., Greathouse, K.L., Safe, S.H., Hung, M.C., Bedford, M.T. and Walker, C.L. Xenoestrogen-induced regulation of EZH2 and histone methylation via estrogen receptor signaling to PI3K/AKT. Mol. Endocrinol. 24:993-1006, 2010. 638. Chadalapaka, G., Jutooru, I., Burghardt, R. and Safe, S. Drugs that target specificity proteins downregulate epidermal growth factor receptor in bladder cancer cells. Mol. Cancer Res. 8:739-750, 2010. 639. Li, X., Mertens-Talcott, S.U., Zhang, S., Kim, K.H., Ball, J. and Safe, S. MicroRNA- 27a indirectly regulates estrogen receptor α expression and hormone responsiveness in MCF-7 breast cancer cells. Endocrinology 151:2462-2473, 2010. 640. Jutooru, I., Chadalapaka, G., Sreevalsan, S., Lei, P., Barhoumi, R., Burghardt, R. and Safe, S. Arsenic trioxide downregulation of specificity protein (Sp) transcription factors in bladder cancer cells is dependent on reactive oxygen species (ROS). Exper. Cell Res. 316:2174-88, 2010. 641. Tsao, T., Kornblau, S., Safe, S., Watt, J.C., Ruvolo, V., Chen, W., Qiu, Y., Coombes, K.R., Ju, Z., Abdelrahim, M., Schober, W., Ling, X., Kardassis, D., Meyer, C., Schimmer, A., Kantarjian, H., Andreeff, M. and Konopleva, M. Role of peroxisome proliferator-activated receptor γ and its coactivator DRIP 205 in cellular responses to CDDO (RTA-401) in acute myelogenous leukemia. Cancer Res. 70:4949-4960, 2010. 642. Jutooru, I., Chadalapaka, G., Abdelrahim, M., Basha, M.R., Samudio, I., Konopleva, M., Andreeff, M. and Safe, S. Methyl 2-cyano-3,12-dioxooleana-1,9-dien-28-oate (CDDO- Me) decreases specificity protein (Sp) transcription factors and inhibits pancreatic

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tumor growth: role of microRNA-27a. Mol. Pharmacol. 78:226-236, 2010. 643. Jutooru, I., Chadalapaka, G., Lei, P. and Safe, S. Inhibition of NFκB and pancreatic cancer cell and tumor growth by curcumin is dependent on specificity protein downregulation. J. Biol. Chem. 285:25332-25344, 2010. 644. Reddivari, L., Vanamala, J., Safe, S.H. and Miller, J.C., Jr. The bioactive compounds α- chaconine and gallic acid in potato extracts decrease survival and induce apoptosis in LNCaP and PC3 prostate cancer cells. Nutr. Cancer 62:601-610, 2010. 645. Pang, X., Zhang, L., Wu, Y., Lin, L., Li, J., Qu, W., Safe, S. and Liu, M. Methyl 2- cyano-3,11-dioxo-18-olean-1,12-dien-30-oate, a derivative of glycyrrhetinic acid, functions as a potent angiogenesis inhibitor. J. Pharmacol. Exp. Ther. 335:172-179, 2010. 646. Roberts, R.A., Smith, R.A., Safe, S., Szabo, C., Tjalkens, R.B. and Robertson, F.M. Toxicological and pathophysiological roles of reactive oxygen and nitrogen species. Toxicology 276:85-94, 2010. 647. Safe, S. 3-Methylcholanthrene induces differential recruitment of aryl hydrocarbon receptor to human promoters. Toxicol. Sci. 117:1-3, 2010. 648. Lee, S.O., Abdelrahim, M., Yoon, K., Chintharlapalli, S., Papineni, S., Kim, K., Wang, H. and Safe, S. Inactivation of the orphan nuclear receptor TR3/Nur77 inhibits pancreatic cancer cell and tumor growth. Cancer Res. 70:6824-36, 2010. 649. Ortholan, C., Durivault, J., Hannoun-Levi, J-M., Guyot, M., Bourcier, C., Ambrosetti, D., Safe, S. and Pages, G. Bevacizumab/docetaxel association is more efficient than docetaxel alone in reducing breast and prostate cancer cell growth: a new paradigm for understanding the therapeutic effect of combined treatment. Eur. J. Cancer 46:3022-3036, 2010. 650. Ichite, N., Chougule, M., Patel, A.R., Jackson, T., Safe, S. and Singh, M. Inhalation delivery of a novel diindolylmethane derivative for the treatment of lung cancer. Mol. Cancer Ther. 9:3003-3014, 2010. 651. Vanderlaag, K., Su, Y., Frankel, A.E., Burghardt, R., Barhoumi, R., Chadalapaka, G., Jutooru, I. and Safe, S. 1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes induce autophagic cell death in estrogen receptor negative breast cancer. BMC Cancer 10:669, 2010. 652. Pathi, S., Jutooru, I., Chadalapaka, G., Sreevalsan, S., Anand, S., Thatcher G. and Safe, S. GT-094, a NO-NSAID, inhibits colon cancer cell growth by activation of a reactive oxygen species (ROS)-microRNA-27a:ZBTB10-specificity protein (Sp) pathway. Mol. Cancer Res. 9:195-202, 2011. 653. Kim, K., Burghardt, R.C., Barhoumi, R., Lee, S.O., Liu, X. and Safe, S. MDM2 regulates estrogen receptor α and estrogen-responsiveness in breast cancer cells. J. Mol. Endocrinol. 46:67-79, 2011. 654. Colon, J., Basha, M.R., Madero-Visbal, R., Konduri, S., Baker, C.H., Herrera, L.J., Safe, S., Sheikh-Hamad, D., Abudayyeh, A., Alvarado, B., Abdelrahim, M. Tolfenamic acid decreases c-Met expression through Sp proteins degradation and inhibits lung cancer cells growth and tumor formation in orthotopic mice. Invest. New Drugs. 29:41- 51, 2011. 655. Basha, R., Baker, C.H., Sankpal, U.T., Ahmad, S., Safe, S., Abbruzzese, J.L. and Abdelrahim, M. Therapeutic applications of NSAIDs in cancer: special emphasis on tolfenamic acid. Front. Biosci. 3:797-805, 2011. 656. Maliakal,P., Abdelrahim, M., Sankpal, U.T., Maliakal, C., Baker, C.H., Safe, S., Herrera, L.J., Abudayyeh, A., Kaja, S., Basha, R. Chemopreventive effects of tolfenamic acid against esophageal tumorigenesis in rats. Invest. New Drugs 30:853- 861, 2011.

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657. Lee, S.O., Li, X., Khan, S. and Safe, S. Targeting NR4A1 (TR3) in cancer cells and tumors. Expert. Opin. Ther. Targets 15:195-206, 2011. 658. Chintharlapalli, S., Papineni, S., Lee, S.O., Lei, P., Jin, U.H., Sherman, S.I., Santarpia, L. and Safe, S. Inhibition of pituitary tumor-transforming gene-1 in thyroid cancer cells by drugs that decrease specificity proteins. Mol. Carcinog. 50:655-667, 2011. 659. Abdelbaqi, K., Lack, N., Guns, E.T., Kotha, L., Safe, S. and Sanderson, J.T. Antiandrogenic and growth inhibitory effects of ring-substituted analogs of 3,3'- diindolylmethane (ring-DIMs) in hormone-responsive LNCaP human prostate cancer cells. Prostate 71:1401-1412, 2011. 660. Yoon, K., Lee, S.O., Cho, S.D., Kim, D., Khan, S. and Safe, S. Activation of nuclear TR3 (NR4A1) by a diindolylmethane analog induces apoptosis and proapoptotic genes in pancreatic cancer cells and tumors. Carcinogenesis 32:836-842, 2011. 661. Barhoumi, R., Mouneimne, Y., Ramos, E., Morisseau, C., Hammock, B.D., Safe, S., Parrish, A.R. and Burghardt, R.C. Multiphoton spectral analysis of benzo[a]pyrene uptake and metabolism in a rat liver cell line. Toxicol. Appl. Pharmacol. 15:45-56, 2011. 662. Shin, J.A., Shim, J.H., Choi, E.S., Leem, D.H., Kwon, K.H., Lee, S.O., Safe, S., Cho, N.P. and Cho, S.D. Chemopreventive effects of synthetic C-substituted diindolylmethanes originating from cruciferous vegetables in human oral cancer cells. Eur. J. Cancer Prev. 20:417-425, 2011. 663. Chintharlapalli, S., Papineni, S., Lei, P., Pathi, S. and Safe, S. Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors. BMC Cancer 11:371, 2011. 664. Pathi, S.S., Lei, P., Sreevalsan, S., Chadalapaka, G., Jutooru, I. and Safe S. Pharmacologic doses of ascorbic acid repress specificity protein (Sp) transcription factors and Sp-regulated genes in colon cancer cells. Nutr. Cancer 63:1133-1142, 2011. 665. Li, Z., Chadalapaka, G., Ramesh, A., Khoshbouei, H., Maguire, M., Safe, S., Rhoades, R.E., Clark, R., Jules G., McCallister, M., Aschner, M. and Hood, D.B. PAH particles perturb prenatal processes and phenotypes: protection from deficits in object discrimination afforded by dampening of brain-oxidoreductase following in utero exposure to inhaled benzo(a)pyrene. Toxicol. Sci. 12:233-247, 2011. 666. Sreevalsan, S., Joseph, S., Jutooru, I., Chadalapaka, G. and Safe, S.H. Induction of apoptosis by cannabinoids in prostate and colon cancer cells is phosphatase dependent. Anticancer Res. 31:3799-3807, 2011. 667. Safe, S., Kim, K., Li, X. and Lee, S. NR4A orphan receptors and cancer. Nucl. Recept. Signal. 9:e002, 2011. 668. Zhang, S., Kim, K., Jin, U.H., Pfent, C., Cao, H., Amendt, B., Liu, X., Wilson-Robles, H. and Safe S.H. Aryl hydrocarbon receptor (AHR) agonists induce micro-RNA-335 expression and inhibit lung metastasis of estrogen receptor negative breast cancer cells. Mol. Cancer Ther. 11:108-118, 2012. 669. Park, Y.Y., Kim, K., Kim S.B., Hennessy, B.T., Kim, S.M., Park, E.S., Lim, J.Y., Li, J., Lu, Y., Gonzalez-Angulo, A.M., Jeong, W., Mills, G.B., Safe, S. and Lee, J.S. Reconstruction of nuclear receptor network reveals that NR2E3 is a novel upstream regulator of ESR1 in breast cancer. EMBO Mol. Med. 4:52-67, 2012. 670. Kim, K., Chadalapaka, G., Lee, S.O., Yamada, D., Sastre-Garau, X., Defossez, P.A., Park, Y.Y., Lee, J.S. and Safe, S. Identification of oncogenic microRNA-17- 92/ZBTB4/specificity protein axis in breast cancer. Oncogene 31:1034-1044, 2012. 671. Chadalapaka, G., Jutooru, I. and Safe, S. Celastrol decreases specificity proteins (Sp) and fibroblast growth factor receptor-3 (FGFR3) in bladder cancer cells. Carcinogenesis 33:886-894, 2012.

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672. Patel, A.R., Spencer, S.D., Chougule, M.B., Safe, S. and Singh, M. Pharmacokinetic evaluation and in vitro-in vivo correlation (IVIVC) of novel methylene-substituted 3,3'- diindolylmethane (DIM). Eur. J. Pharmacol. Sci. 46:8-16, 2012. 673. Li, X., Lee, S.O. and Safe, S. Structure-dependent activation of NR4A2 (Nurr1) by 1,1- bis(3'-indolyl)-1-(aromatic) methane analogs in pancreatic cancer cells. Biochem. Pharmacol. 83:1445-1455, 2012. 674. Lee, S.O., Andey, T., Jin, U.H., Kim, K., Sachdeva, M. and Safe, S. The nuclear receptor TR3 regulates mTORC1 signaling in lung cancer cells expressing wild-type p53. Oncogene 31:3265-3276, 2012. 675. Barchowsky, A., Buckley, L.A., Carlson, G.P., Fitsanakis, V.A., Ford, S.M., Genter, M.B., Germolec, D.R., Leavens, T.L., Leahman-McKeeman, L.D., Safe, S.H., Sulentic, C.E. and Eidemiller, B.J. The Toxicology Education Summit: building the future of toxicology through education. Toxicol. Sci. 127:331-338, 2012. 676. Sankpal, U.T., Abdelrahim, M., Connelly, S.F., Lee, C.M., Madero-Visbal, R., Colon, J., Smith, J., Safe, S., Maliakal, P. and Basha, R. Small molecule tolfenamic acid inhibits PC-3 cell proliferation and invasion in vitro, and tumor growth in orthotopic mouse model for prostate cancer. Prostate 72:1648-1658, 2012. 677. Schulz, V.J., Smit, J.J., Huijgen, V., Bol-Schoenmakers, M., van Roest, M., Kruijssen, L.J., Fiechter, D., Hassing, I., Bleumink, R., Safe, S., van Duursen, M.B., van den Berg, M. and Pieters, R.H. Non-dioxin-like AhR ligands in a mouse peanut allergy model. Toxicol. Sci. 128:92-102, 2012. 678. Wilson, H., Chadalapaka, G., Jutooru, I., Sheppard, S. Pfent C. and Safe, S. Effect of tolfenamic acid on canine cancer cell proliferation, specificity protein (Sp) transcription factors, and Sp-regulated proteins in canine osteosarcoma, mammary carcinoma, and melanoma cells. J. Vet. Intern. Med. 26:977-986, 2012. 679. Liu, X., Jutooru, I., Lei, P., Kim, K., Lee, S.O., Brents, L.K., Prather, P.L. and Safe, S.H. Betulinic acid targets YY1 and ErbB2 through cannabinoid receptor-dependent disruption of microRNA-27a:ZBTB10 in breast cancer. Mol. Cancer Ther. 11:1421- 1431, 2012. 680. Zhuang, G., Meng, C., Guo, X., Cheruku, P.S., Shi, L., Xu, H., Li, H., Wang, G., Evans, A.R., Safe, S., Wu, C. and Zhou, B. A novel regulator of macrophase activation: miR- 223 in obesity associated adipose tissue inflammation. Circulation 125:2892-2903, 2012. 681. Safe, S.H., Prather, P.L., Brents, L.K., Chadalapaka, G. and Jutooru, I. Unifying mechanisms of action of the anticancer activities of triterpenoids and synthetic analogs. Anticancer Agents Med. Chem. 12:1211-1220, 2012. 682. Jin, U.H., Lee, S.O. and Safe, S.H. Aryl hydrocarbon receptor (AhR)-active pharmaceuticals are selective AhR modulators in MDA-MB-468 and BT474 breast cancer cells. J. Pharmacol. Exp. Ther. 343:333-341, 2012. 683. Kim, K., Chadalapaka, G., Pathi, S.S., Jin, U.H., Lee, J.S., Park, Y.Y., Cho, S.G., Chintharlapalli, S. and Safe, S. Induction of the transcriptional repressor ZBTB4 in prostate cancer cells by drug-induced targeting of microRNA-17-92/106b-25 clusters. Mol. Cancer Ther. 11:1852-1862, 2012. 684. Banerjee, N., Talcott, S., Safe, S. and Mertens-Talcott, S.U. Cytotoxicity of pomegranate polyphenolics in breast cancer cells in vitro and vivo: potential role of miRN-27a and miRNA-155 in cell survival and inflammation. Breast Cancer. Res. Treat. 136:21-34, 2012. 685. Pathi S., Jutooru, I., Chadalapaka, G., Nair, V., Lee, S-O. and Safe, S. Aspirin inhibits colon cancer cell and tumor growth and downregulates specificity protein (Sp) transcription factors. PLoS One 7:e48208, 2012. 686. Gandhy, S.U., Kim, K., Larsen, L., Rosengren, R.J. and Safe, S. Curcumin and

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synthetic analogs induce reactive oxygen species and decreases specificity protein (Sp) transcription factors by targeting microRNAs. BMC Cancer 12:564, 2012. 687. Safe, S. Endocrine disruptors and falling sperm counts: lessons learned or not. Asian J. Androl. 15:191-194, 2013. 688. Mertens-Talcott, S.U., Noratto, G.D., Li, X., Anglel-Morales, G., Bertoldi, M.C. and Safe, S. Betulinic acid decreases ER-negative breast cancer cell growth in vitro and in vivo: role of Sp transcription factors and microRNA-27a:ZBTB10. Mol. Carcinog. 52:591-602, 2013. 689. Kim, K., Jutooru, I., Chadalapaka, G., Johnson, G., Frank, J., Burghardt, R., Kim, S. and Safe, S. HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer. Oncogene 32:1616-1625, 2013. 690. Chadalapaka, G., Jutooru, I., Sreevalsan, S., Pathi, S., Kim, K., Chen, C., Crose, L., Linardic, C. and Safe, S. Inhibition of rhabdomyosarcoma cell and tumor growth by targeting specificity protein (Sp) transcription factors. Int. J. Cancer 132:795-806, 2013. 691. Shin, J.A., Jung, J.Y., Ryu, M.H., Safe, S. and Cho, S.D. Mithramycin A inhibits myeloid cell leukemia-1 to induce apoptosis in oral squamous cell carcinomas and tumor xenograft through activation of Bax and oligomerization. Mol. Pharmacol. 83:33-41, 2013. 692. De Miranda, B., Miller, J., Hansen, R., Lunghofer, P., Safe, S., Gustafson, D., Colagiovanni, D. and Tjalkens, R. Neuroprotective efficacy and pharmacokinetic behavior of novel anti-inflammatory para-phenyl substituted diindolylmethanes in a mouse model of Parkinson's disease. J. Pharmacol. Exp. Ther. 345:125-138, 2013. 693. Noratto, G.D., Jutooru, I., Safe, S., Angel-Morales, G. and Mertens-Talcott, S.U. The drug resistance suppression induced by curcuminoids in colon cancer SW-480 cells is mediated by reactive oxygen species-induced disruption of the microRNA-27a-ZBTB10- Sp axis. Mol. Nutr. Food Res. 57:1638-1648, 2013. 694. van den Berg, M., Denison, M.S., Birnbaum, L.S., Devito, M.J., Fiedler, H., Falandysz, J., Rose, M., Schrenk, D., Safe, S., Tohyama, C., Tritscher, A., Tysklind, M. and Peterson, R.E. Polybrominated dibenzo-p-dioxins, dibenzofurans and biphenyls: inclusion in the toxicity equivalency factor concept for dioxin-like compounds. Toxicol. Sci. 133:197-208, 2013. 695. Del Follo-Martinez, A., Banerjee, N., Li, X., Safe, S. and Mertens-Talcott, S. Resveratrol and quercetin in combination have anticancer activity in colon cancer cells and repress oncogenic microRNA-271. Nutr. Cancer 65:494-504, 2013. 696. Bousquet, M., Zhuang, G., Meng, C., Ying, W., Cheruku, P.S., Shie, A.T., Wang, S., Ge, G., Wong, P., Wang, G., Safe, S. and Zhou, B. MiR-150 blocks MLL-AF9 associated leukemia by repressing multiple oncogenes. Mol. Cancer Res. 11:912-922, 2013. 697. Safe, S., Lee, S.O. and Jin, U.H. Role of the aryl hydrocarbon receptor in carcinogenesis and potential as a drug target. Toxicol. Sci. 135:1-16, 2013. 698. Nair, V., Pathi, S., Jutooru, I., Sreevalsan, S., Basha, R., Abdelrahim, M., Samudio, I. and Safe, S. Metformin inhibits pancreatic cancer cell and tumor growth and downregulates Sp transcription factors. Carcinogenesis 34:2870-2879, 2013. 699. Ying, W., Cheruku, P.S., Bazer, F.W., Safe, S.H. and Zhou B. Investigation of macrophage polarization using bone marrow derived macrophages. J. Vis. Exp. 76:e50323, doi: 10.3791/50323, 2013. 700. Andey, T., Patel, A., Jackson, T., Safe, S. and Singh, M. 1,1-Bis(3'indolyl)-1-(p- substituted phenyl) methane compounds inhibit lung cancer cell and tumor growth in a metastasis model. Eur. J. Pharm. Sci. 50:227-241, 2013. 701. Boakye, C.H., Doddapaneni, R., Shah, P.P., Patel, A.R., Godugu, C., Safe, S., Katiyar, S.K. and Singh, M. Chemoprevention of skin cancer with 1,1-bis(3'-indolyl)-1- (aromatic)methane analog through induction of the orphan nuclear receptor, NR4A2

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(Nurr1). PLoS One 8:e69519, 2013. 702. Sreevalsan, S. and Safe, S. The cannabinoid WIN 55,212-2 decreases specificity protein (Sp) transcription factors and the oncogenic cap protein eIF4E in colon cancer cells. Mol. Cancer Ther. 12:2483-2493, 2013. 703. Patel, A.R., Chougule, M.B., Lim, E., Francis, K.P., Safe, S. and Sachdeva, M. Theranostic tumor homing nanocarriers for the treatment of lung cancer. Nanomedicine 10:1053-1063, 2014. 704. Pathi, S., Li, X. and Safe, S. Tolfenamic acid inhibits colon cancer cell and tumor growth and induces degradation of specificity protein (Sp) transcription factors. Mol. Carcinog. 53(S1):E53-E61, 2014. 705. Goldberg, A.A., Titorenko, V.I., Beach, A., Abdelbaqui, K., Safe, S. and Sanderson, J.T. Ring-substituted analogs of 3,3'-diindolylmethane (DIM) induce apoptosis and necrosis androgen-dependent and -independent prostate cancer cells. Invest. New Drugs 32:25- 36, 2014. 706. Safe, S., Jin, U.H., Hedrick, E., Reeder, A. and Lee, S.O. Minireview: Role of orphan nuclear receptors in cancer and potential as drug targets. Mol. Endocrinol. 28:157-172, 2014. 707. Lee, S.O., Jin, U.H., Kang, J.H., Kim, S.B., Guthrie, A.S., Sreevalsan, S., Lee, J.S. and Safe, S. The orphan nuclear receptor NR4A1 (Nur77) regulates oxidative and endoplasmic reticulum stress in pancreatic cancer cells. Mol. Cancer Res. 12:527-538, 2014. 708. Jin, U.H., Lee, S.O., Sridharan, G., Lee, K., Davidson, L.A., Jayaraman A., Chapkin, R., Alaniz, R. and Safe, S.H. Microbiome-derived tryptophan metabolites and their aryl hydrocarbon receptor-dependent agonists and antagonist activities. Mol. Pharmacol. 85:777-788, 2014. 709. Jutooru, I., Guthrie, A.S., Chadalapaka, G., Pathi, S., Kim, K.H., Burghardt, R., Jin, U.H. and Safe, S. Mechanism of action of phenethylisothiocyanate and other ROS-inducing anticancer agents. Mol. Cell. Biol. 34:2382-2395, 2014. 710. Zhang, Z., Kim, K., Li, X., Moreno, M., Sharp, T., Goodheart, M.J., Safe, S., Dupuy, A.J. and Amendt, B.A. MicroRNA-26b represses colon cancer cell proliferation by inhibiting lymphoid enhancer factor 1 (LEF-1) expression. Mol. Cancer Ther. 13:1942-1951, 2014. 711. Safe, S., Imanirad, P., Sreevalsan, S., Nair, V. and Jutooru, I. Transcription factor Sp1, also known as specificity protein 1 as a therapeutic target. Expert Opin. Ther. Targets 18:759-769, 2014. 712. Phillips, T.D., Richardson, M., Cheng, Y.S., He, L., McDonald, T.J., Cizmas, L.H., Safe, S.H., Donnelly, K.C., Wang, F., Moorthy, B. and Zhou, G.D. Mechanistic relationships between hepatic genotoxicity and carcinogenicity in male B6C3F1 mice treated with polycyclic aromatic hydrocarbon mixtures. Arch. Toxicol. In press, 2014. 713. Ying, W., Kanameni, S., Chang, C.A., Nair, V., Safe, S. Bazer, F.W. and Zhou, B. Interferon tau alleviates obesity-induced adipose tissue inflammation and insulin resistance by regulating macrophage polarization. PLoS One 9:e98835, 2014. 714. Jin, U.H., Lee, S.O., Pfent, C. and Safe, S. The aryl hydrocarbon receptor ligand omeprazole inhibits breast cancer cell invasion and metastasis. BMC Cancer 14:498, 2014. 715. Lee, S.O., Li, X., Hedrick, E., Jin, U.H., Tjalkens, R.B., Backos, D.S., Li L., Zhang, Y., Wu, Q. and Safe, S. Diindolylmethane analogs bind NR4A1 and are NR4A1 antagonists in colon cancer cells. Mol. Endocrinol. 28:1729-1739, 2014. 716. Nair, V., Sreevalsan, S., Basha, R., Abdelrahim, M., Abudayyeh, A., Rodrigues Hoffman, A. and Safe, S.H. Mechanism of metformin-dependent inhibition of mTOR and Ras activity in pancreatic cancer: role of Sp transcription factors. J. Biol. Chem. 289:27692-

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27701, 2014. 717. Yang, W.S., Chadalapaka, G., Cho, S.G., Lee, S.O., Jin, U.H., Jutooru, I., Choi, K., Leung, Y.K., Ho, S.M., Safe, S. and Kim, K. The transcriptional repressor ZBTB4 regulates EZH2 through a microRNA-ZBTB4-specificity protein signaling axis. Neoplasia 16:1059-1069, 2014. 718. Phillips, T.D., Richardson, M., Cheng, Y.S., He, L., McDonald, T.J., Cizmas, L.H., Safe, S.H., Donnelly, K.C., Wang, F., Moorthy, B. and Zhou, G.D. Mechanistic relationships between hepatic genotoxicity and carcinogenicity in male B6C3F1 mice treated with polycyclic aromatic hydrocarbon mixtures. Arch. Toxicol. 89:697-977, 2015. 719. De Miranda, B.R., Popichak, K.A., Hammond, S.L., Miller, J.A., Safe, S. and Tjalkens R.B. Novel para-phenyl substituted diindolylmethanes protect against MPTP neurotoxicity and suppress glial activation in a mouse model of Parkinson's disease. Toxicol. Sci. 143:360-373, 2015. 720. Patel, A.R., Godugu, C., Wilson, H., Safe, S. and Singh, M. Evaluation of spray BIO- Max DIM-P in dogs for oral bioavailability and in Nu/nu mice bearing orthotopic/metastatic lung tumor models for anticancer activity. Pharm. Res. In press, 2015. 721. Safe, S. Targeting apoptosis pathways in cancer – Letter. Cancer Prev. Res. 8:338, 2015 722. Jin, U.H., Kim, S.B. and Safe, S. Omeprazole inhibits pancreatic cancer cell invasion through a nongenomic aryl hydrocarbon receptor pathway. Chem. Res. Toxicol. 28:907-918, 2015. 723. DeMiranda, B.R., Popichak, K.A., Hammond. S.L., Jorgensen, B.A., Phillips, A.T., Safe, S. and Tjalkens, R.B. The Nurr1 activator 1,1-bis(3'-indolyl)-1-(p-chlorophenyl)methane blocks inflammatory gene expression in BV-2 microglial cells by inhibiting NFB. Mol. Pharmacol. 87:1021-1034, 2015. 724. Cheng, Y., Jin, U.H., Allred, C.D., Jayaraman, A., Chapkin, R.S. and Safe, S. Aryl hydrocarbon receptor activity of tryptophan metabolites in young adult mouse colonocytes. Drug Metab. Dispos. In press, 2015. 725. Cheng, Y., Jutooru, I., Chadalapaka, G., Corton, J.C. and Safe, S. The long non-coding RNA HOTTIP enhances pancreatic cancer cell proliferation, survival and migration. Oncotarget 6:10840-10852, 2015. 726. Safe, S., Jin, U.H., Morpurgo, B., Abudayyeh, A., Singh, M. and Tjalkens, R.B. Nuclear receptor 4A (NR4A) family – orphans no more. J. Steroid Biochem. Mol. Biol. In press, 2015. 727. Fan, Y.Y., Davidson, L.A., Callaway, E.S., Wright, G.A., Safe, S. and Chapkin, R.S. A bioassay to measure energy metabolism in mouse colonic crypts, organoids and sorted stem cells. Am J Physiol Gastrointest Liver Physiol. 309:G1-G9, 2015. 728. Hedrick, E., Lee, S.O., Kim, G., Abdelrahim, M., Jin, U.H., Safe, S. and Abudayyeh, A. Nuclear receptor 4A1 (NR4A1) as a drug target for renal cell adenocarcinoma. PLoS One 10(6):e0128308, 2015. 729. Patel, A.R., Doddapaneni, R., Andey, T., Wilson, H., Safe, S. and Singh, M. Evaluation of self-emulsified DIM-14 in dogs for oral bioavailability and in Nu/nu mice bearing stem cell lung tumor models for anticancer activity. J Control Release 213:18-26, 2015. 730. Goldberg, A.A., Draz, H., Montes-Grajales, D., Olivero-Verbel, J., Safe, S.H. and Sanderson, J.T. 3,3'-Diindolylmethane (DIM) and its ring-substituted halogenated analogs (ring-DIMs) induce differential mechanisms of survival and death in androgen- dependent and -independent prostate cancer cells. Genes Cancer 6:265-280, 2015. 731. Das Gupta, S., Sae-Tan, S., Wahler, J., So, J.Y., Bak, M.J., Cheng, L.C., Lee, M.J., Lin, Y., Shih, W.J., Shull, J.D., Safe, S., Yang, C.S. and Suh, N. Dietary gamma-tocopherol rich mixture inhibits estrogen-induced mammary tumorigenesis by modulating estrogen

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netabolism, antioxidant response and PPARgamma. Cancer Prev Res (Phila) in press, 2015. 732. Hedrick, E., Crose, L., Linardic, C.M. and Safe, S. Histone deacetylase inhibitors inhibit rhabdomyosarcoma by reactive oxygen species-dependent targeting of specificity protein transcription factors. Mol Cancer Ther in press, 2015. 733. Riddell, N., Jin, U.H., Safe, S.H., Cheng, Y., Chittim, B., Konstantinov, A., Parette, R., Pena-Abaurrea, M., Reiner, E.J., Poirier, D., Stefanac, T., McAlees, A. and McCrindle, R. The characterization and biological potency of mono- to tetra-halogenated carbazoles. Environ Sci Technol in press, 2015. 734. Hedrick, E., Lee, S.O., Doddapaneni, R., Singh, M. and Safe, S. Nuclear receptor 4A1 (NR4A1) as a drug target for breast cancer chemotherapy. Endocr Relat Cancer in press, 2015. 735. Cheng, Y., Jin, U.H., Allred, C.D., Jayraman, A., Chapkin, R.S. and Safe, S. Aryl hydrocarbon receptor activity of tryptophan metabolites in young adult mouse colonocytes. Drug Metab Dispos in press, 2015.

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Books

1. Safe, S. and Hutzinger, O. Mass Spectrometry of Pesticides and Pollutants. Chemical Rubber Co. Press, 1973. 2. Safe, S. and Hutzinger, O. The Chemistry of PCBs. Rubber Co. Press, 1974. 3. Karasek, F.W., Hutzinger, O. and Safe, S. (Editors). Mass Spectrometry in Environmental Sciences, Plenum Press, N.Y. 1985. 4. Safe, S. and Hutzinger, O. (Editors). Environmental Toxin Series, Vol. 1, Polychlorinated Biphenyls (PCBs): Mammalian and Environmental Toxicology, Springer-Verlag Publishing Co., Heidelberg, 1987. 5. Safe, S., Hutzinger, O. and Hill, T.A. (Editors). Environmental Toxin Series, Vol. 3, PCDDs and PCDFs. Polychlorinated Dibenzo- p-dioxins and -furans (PCDDs/PCDFs): Sources and Environmental Impact, Epidemiology, Mechanism of Action, Health Risks. Springer Verlag, Heidelberg, Germany, 1990.

Non-Refereed

1. Hutzinger, O., Safe, S. and Zander, M. Polycyclic Aromatic Hydrocarbons. Analabs Research Notes, 1973. 2. Safe, S., Hutzinger, O., Jamieson, W.D. and Cook, M. The mass and ion kinetic energy spectra of the chlorinated anilines. In Advances in Mass Spectrometry, Vol. 6, Applied Sciences Publishers, 86-91, 1974. 3. Safe, S., Jamieson, W.D. and Hutzinger, O. Ion kinetic energy spectroscopy: a new mass spectrometric technique for the unambiguous identification of isomeric chlorophenols. In Mass Spectrometry and NMR Spectroscopy in Pesticide Chemistry, Plenum Press, pp. 61-70, 1974. 4. Sundstrom, G., Hutzinger, O., Safe, S., Ruzo, L.O. and Jones, D. Methods for the study of metabolism of toxic and persistent chemicals in aquatic organisms as exemplified by chloronaphthalenes. Elsevier Scientific Publishing Co., Amsterdam, pp. 177-188, 1975. 5. Hutzinger, O., Sundstrom, G., Karesek, F. and Safe, S. The chemistry of some potential polyhalogenated water pollutants. In Identification and Analysis of Organic Pollutants in Water (ed. by L.H. Keith) Ann Arbor Science Publishers Inc., pp. 15-33, 1976. 6. Safe, S., Bunce, N., Chittim, B., Hutzinger, O. and Ruzo, L. Photodecomposition of halogenated aromatic compounds. In Identification and Analysis of Organic Pollutants in Water (ed. by L.H. Keith) Ann Arbor Science Publishers Inc., pp. 35-47, 1976. 7. Sundstrom, G., Hutzinger, O., Safe, S. and Platonow, N. The metabolism of p,p'- DDT and p,p'-DDE in the pig. In Fate of Pesticides in Large Animals, Academic Press, NY, pp. 175-182, 1977. 8. Environmental Applications - Mass Spectrometry Specialist Periodical Reports. The Chemical Society, London, England, 6:234-249, 1979. 9. Safe, S. Metabolism, uptake, storage and bioaccumulation of halogenated aromatic pollutants. In Halogenated Biphenyls, Naphthalenes, Dibenzodioxins and Related Products, (R.D. Kimbrough, ed.), Elsevier, Amsterdam, pp. 81-107, 1980. 10. Safe, S. and Wong, A. Effect of polychlorinated biphenyls on unscheduled DNA synthesis and macromolecular binding of benzo[a]pyrene in cultured human skin fibroblasts. In Polynuclear Aromatic Hydrocarbons (M. Cooke and A.J. Dennis, eds.), Batelle Press, Columbia, OH, pp. 467-474, 1981. 11. Safe, S. and Boyd, R.K. Mass spectrometry. In Pesticide Analysis (K.G. Das, ed.), Marcel Dekker, NY, pp. 329-368, 1981.

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12. Parkinson, A., Robertson, L.W. and Safe, S. Further characterization and applications of the 4-chlorobiphenyls hydroxylase assay. In Biological Reactive Intermediates, Plenum Press, NY, pp. 753-759, 1981. 13. Parkinson, A. and Safe, S. The cytochrome P-450-mediated metabolism of biphenyl and the 4-halobiphenyls. In Biological Reactive Intermediate, Plenum Press, NY, pp. 745-752, 1982. 14. Safe, S., Parkinson, A., Robertson, L., Cockerline, R. and Safe, L. PCBs as microsomal enzyme inducers: structure-activity rules. In Health Effects of Halogenated Hydrocarbons, Pergamon Press, Oxford, pp. 106-119, 1982. 15. Safe, S., Campbell, M.A., Lambert, I. and Copp, L. Polychlorinated biphenyls as phenobarbitone-type inducers: structure-activity correlations in cytochrome P-450. In Biochemistry, Biophysics and Environmental Implications (ed. Hietanen, Latinen and Hanninen), Elsevier, Biomedical Press, Amsterdam, pp. 341-343, 1982. 16. Safe, S., Parkinson, A., Robertson, L., Bandiera, S., Sawyer, T., Safe, L., Lambert, I., Andres, J. and Campbell, M.A. Halogenated biphenyls as AHH inducers: effects of different halogen substituents in cytochrome P-450. In Biochemistry, Biophysics and Environmental Implications (ed., Heitanen, Laitinen and Hanninen), Elsevier Biomedical Press, Amsterdam, pp. 441-443, 1982. 17. Safe, S., Parkinson, A., Robertson, L., Safe, S. and Bandiera, S. Polychlorinated biphenyls: effects of structure on biologic and toxic activity. Workshop on the Combined Effects of Zenobiotics, NRCC No. 18978, Ottawa, Canada, pp. 151-176, 1982. 18. Safe, S., Robertson, L., Parkinson, A., Schilling, M., Cockerline, R. and Campbell, M.A. Polybrominated biphenyls, polychlorinated naphthalenes and polychlorinated terphenyls as microsomal enzyme inducers. In Health Effects of Halogenated Hydrocarbons, Pergamon Press, Oxford, pp. 97-105, 1982. 19 Safe, S., Mullin, M., Safe, L., Pochini, C., McCrindle, S. and Romkes, M. High resolution PCB analysis. In Physical Behavior of PCBs on the Great Lakes, Ann Arbor Science, pp. 1-13, 1983. 20. Safe, S., Robertson, L., Sawyer, T., Parkinson, A., Bandiera, S., Safe, L. and Campbell, M. PCDDs and Related Compounds. In Metabolism and Biochemistry in Human and Environmental Risks of Chlorinated Dioxins and Related Compounds, (ed. Tucker, Young and Gray), Plenum Publishing Corp., pp. 393-403, 1983. 21. Mullin, M.D., Pochini, C.M., Safe, S.H. and Safe, L.M. Analysis of PCBs using specific isomer high resolution capillary gas chromatography. In PCBs: Human and Environmental Hazards, (Itri, F.M. and Kamrin, M.A., ed.), Butterworth Publishers, Boston, pp. 165-176, 1983. 22. Safe, S. Microbial degradation of polychlorinated biphenyls. In Biochemistry of Microbial Degradation of Organic Compounds (D.T. Gibson, ed.), Marcel Dekker, NY, pp. 361-369, 1984. 23. Safe, S., Sawyer, T., Bandiera, S., Safe, L., Zmudzka, B., Mason, G., Romkes, M., Denomme, M.A. and Fujita, T. Binding to the 2,3,7,8-TCDD receptor and AHH/EROD induction: in vitro QSAR. Banbury Report (ed. A. Poland), Cold Spring Harbor Laboratory, No 18, pp. 135-149, 1984. 24. Safe, S.H. Reviews in biochemical toxicology. Vol. 5. Pesticide Biochem. and Physiol. 21:417- 418, 1984. 25. Hutzinger, O., Berg, M.V.D., Olie, K., Opperhuizen, A. and Safe, S. Dioxins and furans in the environments: evaluating toxicological risk from different sources by multi- criteria analysis. In Dioxins and Furans in the Environment (M. Kamrin, ed.), Hemisphere Publishing Corp., pp. 9-32, 1985. 26. Safe, S. Polychlorinated biphenyls. In Carcinogens and Mutagens in the Environment

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(Stich, H. Ed.), Vol. V, CRC Press, Boca Raton, FL, pp. 101-113, 1985. 27. Safe, S. Polychlorinated biphenyls: problems and progress in hazardous contaminants in Ontario. In Human and Environmental Effects (T.C. Hutchison and S.M. Evans, eds), Institute for Environmental Studies, Toronto, pp. 60-68, 1985. 28. Safe, S. PCBs and human health. In Polychlorinated Biphenyls (PCBs): Mammalian and Environmental Toxicology, Springer-Verlag Publishing Co., Heidelberg, Vol 1, pp. 1-13, 1987. 29. Parkinson, A. and Safe, S. Mammalian biologic and toxic effects of PCBs. In Polychlorinated Biphenyls (PCBs): Mammalian and Environmental Toxicology, Springer-Verlag Publishing Co., Heidelberg, Vol 1, pp. 49-75, 1987. 30. Safe, S., Safe, L. and Mullin, M. Polychlorinated biphenyls: environmental occurrence and analysis. In Polychlorinated Biphenyls (PCBs): Mammalian and Environmental Toxicology, Springer-Verlag Publishing Co., Heidelberg, Vol 1, pp. 133-145, 1987. 31. Safe, S. Polyhalogenated aromatics: uptake, disposition and metabolism. In Halogenated Biphenyls, Naphthalenes, Dibenzodioxins and Related Compounds, 2nd Edition, Elsevier-North Holland, Amsterdam, pp. 51-69, 1989. 32. Goldstein, J.A. and Safe, S. Mechanism of action and structure-activity relationships for the chlorinated dibenzo-p-dioxins and related compounds. In Halogenated Biphenyls, Naphthalenes, Dibenzodioxins and Related Compounds, 2nd Edition, Elsevier-North Holland, Amsterdam, pp. 239-293, 1989. 33. Safe, S. and Sparling, J. Other industrial pollutants and natural toxins. In Mass Spectrometry in Environmental Sciences (ed., Karasek, F.W., Hutzinger, O. and Safe, S.) Plenum Press, New York, in press, 1989. 34. Safe, S.: Polychlorinated biphenyls: human health effects. In Hazards, Decontamination and Replacement of PCBs, Plenum Press, New York, in press, 1989. 35. Safe, S. Polychlorinated dibenzofurans: environmental impact, toxicology and hazard assessment. In Hazard Assessment of Chemicals - Current Developments (J. Saxena, ed.) Vol. 7, Hemisphere Publishing Co., Washington, 7:283-327, 1990. 36. Safe, S. and Hutzinger, O. PCDDs and PCDFs: sources and environmental impact. In Polychlorinated Dibenzo-p-dioxins and -furans (PCDDs/PCDFs): Sources and Environmental Impact, Epidemiology, Mechanisms of Action, Health Risks. Environmental Toxin Series, Vol. 3, Springer Verlag, Heidelberg, Germany. pp. 1-20, 1990. 37. Safe, S., Gasiewicz, T.A. and Whitlock, Jr., J.P. Mechanism of action. In Polychlorinated Dibenzo-p-dioxins and -furans (PCDDs/PCDFs): Sources and Environmental Impact, Epidemiology, Mechanisms of Action, Health Risks. Environmental Toxin Series, Vol. 3, Springer Verlag, Heidelberg, Germany. pp. 61-91, 1990. 38. Safe, S. Development, validation and limitations of toxic equivalency factors. In Current Views on the Impact of Dioxins and Furans in Human Health and the Environment, Toxicology Forum, Inc., Washington, DC. pp. 176-180, 1993. 39. Safe, S. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-induced modulation of endocrine response pathways. In Current Views on the Impact of Dioxins and Furans in Human Health and the Environment, Toxicology Forum, Inc., Washington, DC. pp. 316-333, 1993. 40. Safe, S. Chlorocarbons - hydrocarbons (toxicology). In Kirk-Othmer Encyclopedia of Chemical Technology, 4th ed., Vol. 6, John Wiley and Sons, NY. pp. 127-139, 1993. 41. Safe, S. Assessing the role of environmental estrogens in human reproductive health. Health and Environ. Digest. 8:79-81, 1995. 42. Safe, S.H., Chen, I. and Porter, W. Dietary indoles with antiestrogenic activity in common vegetables and their implications. In: Estrogens, Progestins and Their

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Antagonists (E. Pavlik, ed.), Birkhouser, Boston. pp. 73-97, 1996. 43. Safe, S. Human toxicology of chlorinated organic micropollutants. In: Chlorinated Organic Micropollutants (R.M. Harrison, ed.), Royal Society of Chemistry Publications, Cambridge. pp. 73-88, 1996. 44. Safe, S. and Zacharewski, T. Organochlorine exposure and risk for breast cancer. In: Etiology of Breast and Gynecological Cancers, pp. 133-145, 1997. 45. Safe, S. and McDougal, A. Environmental factors and breast cancer. In: Endocrine- Related Cancers (A. Howell, ed.) J. Endocrinol. 4:1-11, 1997. 46. Safe, S. Is there an association between environmental estrogens and breast cancer? Environ. Health Persp. 105(Suppl. 3):675-678, 1997. 47. Hoivik, D.J., Safe, S.H. and Gaido, K.W. Effects of xenobiotics on hormone receptors. In: Toxicant-Receptor Interactions (M.S. Denison and W.G. Helferich, eds.), Taylor & Francis, Bristol, PA, pp. 53-68, 1998. 48. Zacharewski, T. and Safe, S. Antiestrogenic activity of TCDD and related compounds. In: Reproductive and Developmental Toxicology (K.S. Korach, ed.), Marcel Dekker, Inc., New York. pp. 431-448, 1998. 49. Hoivik, D. and Safe, S. Polychlorinated biphenyls. In: Environmental and Occupational Medicine, (W.N. Rom, ed.), Lippincott-Raven, Philadelphia. pp. 1205- 1214, 1998. 50. Connor, K., Howell, J., Safe, S., Chen, I., Liu, H., Berhane, K., Sciarretta, C. and Zacharewski, T. Failure of chloro-s-triazine-derived compounds to induce estrogenic responses in vivo and in vitro. In: Triazine Herbicide Risk Assessment (L.G. Ballentine, J.E. McFarland, D.S. Machett, eds.), ACS Symposium Series 683, Washington, D.C. pp. 424-431, 1998. 51. Gaido, K.W., Maness, S.C., Leonard, L., Gould, J., Connor, K., Safe, S. and McDonnell, D.P. In vitro methods for characterizing chemical interactions with steroid receptors. In: Human Diet and Endocrine Modulation (G.E. Dunaif, S.S. Olin, J. Scimeca and J.A. Thomas, eds.), ILSI Press, Washington, D.C. pp. 85-94, 1998. 52. Safe, S. and Ramamoorthy, K. Disruptive behavior. In: Forum for Applied Research and Public Policy, University of Tennessee, Knoxville. pp. 19-23, 1998. 53. Safe, S. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related environmental antiestrogens: characterization and mechanism of action. In: Endocrine Disruptors (R.K. Naz, ed.), CRC Press, Boca Raton, FL. pp. 187-221, 1999. 54. Safe, S. Environmental estrogens. In: Encyclopedia of Reproduction (E. Knobil and J.D. Neill, eds.), Academic Press, NY. Vol. 1, pp. 1100-1103, 1999. 55. Porter, W. and Safe, S. Estrogenic and antiestrogenic compounds. In: Molecular Biology Approaches to Toxicology (A. Puga and Wallace, K.B., eds.), Techbooks, Fairfax, VA. pp. 267-283, 1998. 56. Goldstein, L.S., Weyand, E.H., Safe, S., Steinberg, M., Culp, S.J., Gaylor, D.W., Beland, F.A. and Rodriguez, L.V. Tumors and DNA adducts in mice exposed to benzo[a]pyrene and coal tars: implications for risk assessment. Environ. Health Perspect. 106(Suppl 6):1325-1330, 1998. 57. Gaido, K., Dohme, L., Wang, F., Chen, I., Blankvoort, B., Ramamoorthy, K. and Safe, S. Comparative estrogenic activity of wine extracts and organochlorine pesticide residues in food. Environ. Health Perspect. 106(Suppl 6):1347-1351, 1998. 58. Safe, S. Toxic equivalency factors and their use in hazard and risk assessment. In: Toxicology (H. Marquardt, S.G. Schafer, R.O. McClellan and F. Welsch, eds.), Academic Press, San Diego. pp. 1191-1197, 1999. 59. Safe, S. Chemically-induced oestrogenic and anti-oestrogenic activity: structure- dependent effects and molecular mechanisms of action. In: Endocrine and Hormonal Toxicology (P.W. Harvey, K.C. Rush and A. Cockburn, eds.), John Wiley and Sons, Ltd.

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pp. 461-485, 1999. 60. Safe, S. Endocrine Disruptors: New Toxic Menace? In: Earth Report 2000: Revisiting the True State of the Planet (R. Bailey, ed.), McGraw Hill, New York. pp. 189- 202, 2000. 61. Safe, S. Xenoestrogens and human health. Is there a problem? The argument against. Progr. Environ. Sci. 21:21-30, 2000. 62. Safe, S. Reproductive effects: endocrine disruption. In: Risk Assessment in the Food Chain of Children (P.J. Aggett and H.A. Kuiper, eds.), Nestle Nutrition Workshop Series, Paediatric Programme, Vol. 44, Nestec Ltd., Vevey/Lippincott Williams & Wilkins, Philadelphia, 2000. 63. Safe, S. Bisphenol A and related endocrine disrupters. Toxicol. Sci. 56:251-252, 2000. 64. Safe, S. Toxicology of persistent organic pollutants. Eur. J. Lipid Sci. Technol. 102:52-53, 2000. 65. Safe, S. PCBs as aryl hydrocarbon receptor agonists: implications for risk assessment. In: PCBs: Recent Advances in the Environmental Toxicology and Health Effects, The University Press of Kentucky, pp. 171-178, 2001. 66. Gaido, K.W., McDonnell, D.P and Safe, S. In vitro methods for characterizing chemical interactions with steroid hormone receptors. In: Handbook of Environmental Chemistry (M. Metzler, ed.), pp. 28-38, 2001. 67. Safe, S. Transcriptional activation of genes by 17β-estradiol through estrogen receptor-Sp1 interactions. In: Vitamins and Hormones - Advances in Research and Applications, Vol. 62, pp. 231-252, 2001. 68. Safe, S. Hydroxylated polychlorinated biphenyls (PCBs) and organochlorine pesticides as potential endocrine disruptors. In: Handbook of Environmental Chemistry (M. Metzler, ed.) pp. 155-167, 2001. 69. Safe, S. Saville, B. and Stoner, M. Sp1 and Sp3 transcription factors. In: Wiley Encyclopedia of Molecular Medicine.. Vol. 5, John Wiley and Sons, New York, NY. pp. 2959-2961, 2002. 70. Safe, S. Exposure to POPs and other congeners. In: Biomarkers of Environmentally Associated Disease (S.H. Wilson and W.A. Suk, eds), Lewis Publishers, Boca Raton, FL pp. 455-470, 2002. 71. Winston, G.W., Adams, S.M., Benson, W.H., Gray, L.E., Matthews, H.B., Moore, M.N. and Safe, S.H. Biological bases of similarities and differences. In: Interconnections Between Human Health and Ecological Integrity (R.T. Di Giulio and W.H. Benson, eds.), SETAC Press, Pensacola, FL. pp. 43-63, 2002. 72. Safe, S. Toxicology and risk assessment of POPs. In: The Handbook of Environmental Chemistry (H. Fiedler, ed), Vol. 3, Part O, Springer Verlag, Heidelberg. pp. 224-235, 2002. 73. Avakian, M.D., Dellinger, B.; Fiedler, H., Gullet, B., Koshland, C., Marklund, S., Oberdorster, G., Safe, S., Sarofim, A., Smith, K.R., Schwartz, D. and Suk, W.A. The origin, fate, and health effects of combustion by-products: a research framework. Environ. Health Persp. 110:1155-1662, 2002. 74. Safe, S., Pallaroni, L., Yoon, K., Gaido, K., Ross, S. and McDonnell, D. Problems for risk assessment of endocrine-active estrogenic compounds. Environ. Health Perspect. 110(S):925- 929, 2002. 75. Safe, S. Environmental estrogens: roles in male reproductive tract problems and in breast cancer. Rev. Environ. Health 17:253-262, 2002. 76. Safe, S., Wormke, M., Walker, K., Dickerson, R. and Castro-River, E. Estrogen receptor signaling and crosstalk with the Ah receptor in endometrial cancer cells. In: Cell and Molecular Biology of Endometrial Carcinoma (H. Kuramoto and M. Nishida, eds.), Springer Verlag, Tokyo, pp. 109-122, 2003.

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77. Safe, S. Cadmium's disguise dupes the estrogen receptor. Nature Medicine 9:1000- 1001, 2003. 78. Safe, S. Endocrine disruptors. In: Politicizing Science (M. Gough, ed.), Hoover Institution Press, Stanford, CA. pp. 91-115, 2003. 79. Safe, S. Estrogen receptor actions through other transcription factor sites. In: Encyclopedia of Hormones (H.L. Henry and A.W. Norman, eds.), pp. 591-594, 2003. 80. Donnelly, K.C., Suk, W. and Safe, S.H. The Superfund Basic Research Program: a model for interdisciplinary research to reduce risk and prevent exposure. In: Defense and the Environment: Effective Scientific Communication (K. Mahutova et al., eds.), Kluwer Academic Publishers, The Netherlands, pp. 197-203, 2004. 81. Safe, S. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related environmental antiestrogens: characterization and mechanism of action. In: Endocrine Disruptors 2nd Edition (R.K. Naz, ed.), CRC Press, Boca Raton, FL, pp. 249-284, 2005. 82. Safe, S. Polychlorinated biphenyls. In: Environmental and Occupational Medicine, 4th ed. (W. Rom, ed.), Lippincott-Raven Publishers, Philadelphia, pp. 1203-1212, 2007. 83. Safe, S., Khan, S., Li, X. and Wu, F. Chemical induced estrogenicity. In: Veterinary Toxicology (R.C. Gupta, ed.), Elsevier, New York, pp. 811-822, 2007. 84. Safe, S., Jutooru, I. and Chadalapaka, G. Estrogenic endocrine disruptors: molecular characteristics and human impacts. In Comprehensive Toxicology, 2nd Ed, (ed. McQueen, C.), Elsevier, Amsterdam, pp. 609-621, 2010. 85. Safe, S., Chadalapaka, G. and Jutooru, I. Aryl hydrocarbon receptor ligands: toxic, biochemical and therapeutic effects. In Endocrine Toxicology (eds. Eldridge, J.C. and Stevens, J.T.), Taylor and Francis Publishers, pp. 189-209, 2010. 86. Safe, S., Chadalapaka, G., Jutooru, I., Chintharlapalli, S. and Papineni, S. Highlights of pentacyclic triterpenoids in the cancer setting. In: Pentacyclic Triterpenoids as Promising Agents in Cancer (ed. Salvador, J.A.R.), Nova Science Publishers, Hauppauge, NY, pp. 277-306, 2010. 87. Safe, S., Walker, K. and Zhang, S. Dioxin as an environmental pollutant and its role in breast cancer. In: Environment and Breast Cancer (ed. Russo, J.), Springer Sciences, Heidelburg, pp. 127-146, 2011. 88. Safe, S., Chadalapaka, G. and Jutooru, I. AHR-reactive compounds in the human diet. In: The Ah Receptor in Biology and Toxicology (ed. Pohjanvirta, R.), John Wiley and Sons, Hoboken, NJ. pp. 331-342, 2012. 89. Safe, S. RNA interference. In: Brenner's Encyclopedia of Genetics, 2nd Edition, Volume 6, pp. 288-289, 2013. 90. Safe, S. Natural products as inducer of apoptosis – Letter. Cancer Prev. Res. In press, 2015.

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