CYTOCHROME P450 Biochemistry, Biophysics and Molecular Biology

8th International Conference Lisbon, Portugal 24-28 October 1993

Edited by:

Gulbenkian Institute of Science

JohnLibbey ra JEUROTEXT CONTENTS

V Preface VII Committee VIII Acknowledgements IX Foreword

EVOLUTION AND PHYLOGENETIC DIVERSITY OF P450 GENES

3 Evolutionary argument for a connection between drug metabolism and signal transaction. D.W. NEBERT, R. FEYEREISEN

15 Hierarchical clustering and proposed classification of the P450 superfamily using consensus sequences. A.I. ARCHAKOV, K.N. DEGTYARENKO

23 Function and diversity of plant cytochrome P450. F. DURST, I. BENVENISTE, J.-P. SALAUN, D. WERCK

31 Insect cytochrome P450: functions, regulation and diversify. R. FEYEREISEN, J.F. ANDERSEN, F.A. CARINO, M.B. COHEN, J.F. KOENER, S. REPECKO, J.A SCOTT, M.J. SNYDER

37 The role of conserved 5'-flanking (Barbie Box) DNA sequences and barbi- turate-responsive DNA-binding proteins in the mechanism of induction by barbiturates of P450 cytochromes in Bacillus megaterium and other proka- ryotic and eukaryotic organisms. A.J. FULCO, J.-S. HE, Q. LIANG

43 Nitric oxide synfhase: mechanisms and relationship to cytochrome P450. K.A. WHITE, R.A. PUFAHL, N.M. OLKEN, J.M. HEVEL, M.K. RICHARDS, M.A. MARLETTA

XI II CONTROL MECHANISMS I—-I IN THE BIOGENESIS OF CYTOCHROME P450'S

51 Growth hormone regulation of liver sexual differentiation. J.A. GUSTAFSSON, P. TOLLET, A. MODE

59 Mechanisms of liver-specific expression of the CYP2D5 gene. Y.-H. LEE, F.J. GONZALEZ

67 Expression and function of Ad4BP, a steroidogenic cell-specific transcription factor. K.-l. MOROHASHI, S.-l. HONDA, M. NOMURA, K. TAKAYAMA, M. HARA, T. OMURA

75 DNA-binding regulatory factors and inducible expression of the P4501A1 gene. K. SOGAWA, N. MATSUSHITA, M. EMA, Y. FUJII-KURIYAMA

81 Induction of brain P450 by solvents and pharmaceuticals. M. WARNER, M. STROMSTEDT, A. WYSS, S. YOSHIDA, J.A. GUSTAFSSON

89 Hormonal influence on developmental changes in hepatic P450 in rat liver. Y. YAMAZOE, N. MURAYAMA, M. SHIMADA, K. NAGATA, H. ISHIKAWA, H. HASHIMOTO, K. NAKAYAMA, K. SOGAWA, Y. FUJII-KURIYAMA, R. KATO

97 Mechanisms of enhancement and inhibition of cytochrome P450 catalytic activities. F.P. GUENGERICH, B.-R. KIM, E.M.J. GILLAM, T. SHIMADA

103 Role of individual human liver P450s and other enzymes in anti-cancer drug metabolism: drug activation and drug resistance mechanisms. T.K.H. CHANG, G. CHEN, D.J. WAXMAN

109 Comparative analysis of cytochrome P450 3A expression in cultures of rat, rabbit and human hepatocytes. P.S. GUZELIAN

115 Receptor-dependent coregulation of CYP4A genes and peroxisome proliferation. G.G. GIBSON

121 Phenobarbital induction of P450 cytochromes in rat liver: genetic and endocrine control of a common regulatory mechanism. M. LARSEN, F. IKEGWUONU, P. BRAKE, C. JEFCOATE

XII 125 Structural and functional characteristics of CYP3A genes related to the development-dependent phenotypic expression and induction by Dexame- thasone. M.C. LECHNER, M.M. TELHADA, V. RIBEIRO, T.M. PEREIRA, MJ. GAMA

129 Expression of xenobiotic-metabolizing cytochrome P450 forms in human adult and fetal liver. J. HAKKOLA, M. PASANEN, R. PURKUNEN, S. SAARIKOSKI, O. PELKONEN, J. MAENPAA, A. RANE, H. RAUNIO

133 Transcriptional regulation of CYP2B1 /B2 gene in rat liver. G. PADMANABAN, C. NIRODI, L PRABHU, N. RAM, S. SULTANA

137 Identification of DNA sequences involved in basal and phenobarbital induced transcription of a CYP2B2 gene. A. SHERVINGTON, I.R. PHILLIPS, E.A. SHEPHARD

141 Tissue-specific expression of cytochrome P450arom gene by alternative use of multiple exons 1 and promoters, and a switching of tissue-specific exons 1. N. HARADA, S.-l. HONDA, Y. TAKAGI

in CYTOCHROME P450 III I IN CANCER AND IN IMMUNOTOXYCOLOGY

147 Importance of individual enzymes in the control of ultimate carcinogens. F. OESCH, B. OESCH-BARTLOMOWICZ, H. GLATT, K.-L PLATT, M. ARAND

155 Genetic polymorphism of P450 and human cancer. K. KAWAJIRI, J. WATANABE, S.-l. HAYASHI

163 Polymorphisms of cytochrome P450 CYP2D6 as risk factor in carcinogene- sis. U.A. MEYER

173 CYP1A1 -dependent benzo[a]pyrene metabolism activates genes regulated by the human immunodeficiency virus 1 long terminal repeat DNA sequences. A. PUGA, Y. YAO

183 Cytochrome P450 2B4 antigenic determinants revealed by pepscan. E.F. KOLESANOVA, S.A. KOZIN, A.I. ARCHAKOV

XIII 189 Specificity of covalent binding and autoantibodies in drug-induced immu- noallergic hepatotoxicity. S. LECOEUR, D. CHALLINE, J.C. GAUTIER, F. BALLET, P. BEAUNE

193 Metabolic activation of the thiophene ring as a primary event in immuno- allergic hepatitis to tienilic acid. P.M. DANSETTE, M.P. LOPEZ-GARCIA, C. AMAR, C. PONS, P. VALADON, E. BONIERBALE, PH. BEAUNE, J.C. HOMBERG, D. MANSUY

197 Anti-cytochrome P450 antibodies in patients with aromatic anticonvulsant- induced hypersensitivity reactions. J.S. LEEDER, V.A. COOK, R.J. RILEY

201 Presence of cytochrome P450 on human hepatocyte plasma membrane. Recognition by several autoantibodies. J. LOEPER, V. DESCATOIRE, M. MAURICE, P. BEAUNE, G. FELDMANN, F.P. GUENGERICH, D. PESSAYRE

205 Activation of promutagens by rat CYP P450 expressing V79 cells. A.S. RODRIGUES, I. DUARTE SILVA, M.J. MONTEIRO, H. CARIA, A. LAIRES, T. CHAVECA, J. RUEFF

209 P450 and azole tolerance in fungi. S.L KELLY, D.C. LAMB, B.C. BALDWIN, D.E. KELLY

213 Cytochrome P4502E1-dependent metabolism as a biomarker for genetic susceptibility to chemically-induced cancers: a pilot study. S.L. CAMPLEMAN, S.J. TAMAKI, B.-A. HOENER, M.T. SMITH

217 Comparison of the principal drug-metabolizing enzyme systems in human tumors and corresponding peritumoral tissues: importance for sensitivity and/or resistance to anticancer drugs. G.G. CHABOT, L. MASSAAD, C. TOUSSAINT, N. ALBIN, O. PARISE, V. RIBRAG, F. JANOT, A. GOUYETTE

BIOTECHNOLOGY AND NOVEL P450 FUNCTIONS. FROM IV BASIC P450 RESEARCH TO APPLICATIONS IN DRUG DESIGN 225 Molecular engineering steroid hydroxylase activity of mammalian P450s. M. NEGISHI, M. IWASAKI, T. SUEYOSHI, T.A DARDEN, L.G. PEDERSEN

233 Co-expression of mammalian, plant or yeast P450s and P450 reductases in Saccharomyces cerevisiae as cloning and bioconversion tools. D. POMPON, G. TRUAN, A. BELLAMINE, M. KAZMAIER, P. URBAN

XIV 241 Expression in E. coli of enzymatically active fusion proteins containing cytochrome P450 and cytochrome P450 reductase. C.W. FISHER, M.S. SHET, P.L HOLMANS, R.W. ESTABROOK

249 The role of P450s in insect-plant interactions. H. PRAPAIPONG, C.-F. HUNG, M.R. BERENBAUM, M.A. SCHULER

257 From basic cytochrome P450 research to applications in drug development. A.Y.H. LU

i 1 BIOSYNTHESIS AND MEMBRANE TOPOLOGY OF MICROSOMAL P450. 1 V 1 FUNCTIONAL IMPLICATIONS OF P450 STRUCTURE

265 Biosynthesis and membrane topology of microsoma! cyiochrome P450. M. SAKAGUCHI, K. MIHARA, T. OMURA

271 Structure and function in P450s: are bacterial P450s good models for eukaryotic P450s? J.A. PETERSON, J.DEISENHOFER, C. HASEMANN, K.G. RAVICHAN- DRAN, S.S. BODDUPALLI, S. GRAHAM-LORENCE

279 Structural and functional mapping of P450 proteins inferred from multiple sequence alignment. O. GOTOH

285 Role of the NH2-ferminal region of microsomal P450s in catalysis and membrane binding. S.J. PERNECKY, V.S. FUJITA, L.L BESTERVELT, M.J. COON

293 Structure-function analysis of eukaryotic P450s expressed in E. col!. I.A. PIKULEVA, CM. JENKINS, M.R. WATERMAN

299 Proton and electron transfer mechanism in dioxygen activation by cytochrome P450cam. H. SHIMADA, R. MAKINO, M. UNNO, T. HORIUCHI, Y. ISHIMURA

307 High level expression of integral membrane proteins induces proliferation of the endoplasmic reticulum. R. MENZEL, E. KARGEL, C. WOLFF, F VOGEL, W.-H. SCHUNK

311 Membrane topology and complex formation of cytochrome P450SCC in proteoliposomes studied by delayed fluorescence depolarization. D. SCHWARZ, A. CHERNOGOLOV, V. KROGER, S. USANOV, A. STIER

XV 315 Core glycosylafion of cytochrome P450(arom): evidence for localization of N-terminus of microsomal cytochrome P450 in the lumen. O. SHIMOZAWA, M. SAKAGUCHI, H. OGAWA, N. HARADA, K. MIHARA, T. OMURA

319 Systematic analysis of N-terminal transmembrane segments of microsomal P450s. K.N. DEGTYARENKO, A.I. ARCHAKOV

323 Membrane topology of P450c21. L.-C. HSU, B.-C. CHUNG

327 Study of the membrane topology and functional importance of the central region of cytochrome P450scc (CYP11A1) molecule by selective chemical modification of Cys264. A. CHERNOGOLOV; S. USANOV, R. KRAFT, D. SCHWARZ

DETERMINANTS OF COMPONENT INTERACTIONS IN P450 VI SYSTEMS. ELECTRON TRANSFER AND OXYGEN ACTIVATION 333 The importance of one-electron transfers in the mechanism of cytochrome P450. R.E. WHITE

341 Studies of the interactions of microsomal cytochrome P450 reductase with cytochromes P450. H.W STROBEL, S. SHEN

349 On the nature of the NADPH-cytochrome P450 reductase-cytochrome P450 electron transfer complex. A.I. VOZNESENSKY, J.B. SCHENKMAN

357 Electron pathways in adrenal mitochondrial cytochrome P450 systems: relative rates of leakage and hydroxylation. R. RAPOPORT, M. RAIKHINSTEIN, D. SKLAN, I. HANUKOGLU

365 Reaction mechanism of P450 dependent steroidogenesis: regulation of catalytic activity of bovine adrenal P450 (11 (3) S. TAKEMORI, S. KOMINAM1, S.I. 1KUSHIRO, T. YAMAZAKI, D. HARADA

373 Electron transfer associated dioxygen activation in P450 systems S.G. SUGAR, J. AIKENS, N. GERBER, M. MCLEAN, K. SUSLICK, D. BENSON

XVI 379 Conformational control of interprotein electron transfer. F. MILLETT, B. DURHAM, A. WILLIE, S. HAHM, L. GEREN, R. LIU, P. STAYTON, M. McLEAN, M. MILLER, S. SUGAR, G. PEILAK, J. KRAUT

387 Studies on electron transfer pathways in cytochrome P450 systems. R. BERNHARDT, V. BECKERT, H. UHLMANN, S.G. SUGAR

395 Electron transfer and protein-protein interactions in soluble reconstituted liver monooxygenase systems. G.I. BACHMANOVA, I.P. KANAEVA, I.F. SEVRUKOVA, O.V. NIKITYUK, N.V. STEPANOVA, TV. KNUSHKO, Y.M. KOEN, A.I. ARCHAKOV

403 Thermodynamic and kinetic studies of the process of camphor entry into cytochrome P450cam. G. HUI BON HOA, E. DEPREZ

409 Cytochrome P450: topology and catalysis. P.R. ORTIZ DE MONTELLANO, N. SHIRANE, Z. SUI, J. FRUETEL, J.A. PETERSON, JJ. DE VOSS

417 Conclusive evidence of a quarternary cluster model for cholesterol side chain cleavage reaction catalyzed by cytochrome P-450scc. T. HARA, M. TAKESHIMA

421 Structural features of the bovine mitochondrial electron transfer system CYP11A1. R.-J. KUBAN, A. MARG, K. RUCKPAUL

425 An integrated*, phase-theoretic approach to cytochrome P450cl7 (CYP17) catalysis: probabilities of hydroxyprogesterone stabilization vs decomposi- tion depend on reductase "arrival" frequencies in stochastic relation to intermediate "departure" frequencies at the active site. W.N. KUHN-VELTEN

429 Kinetic studies on a genetically engineered fused enzyme between rat cytochrome P4501 Al and yeast NADPH-P450 reductase. T. SAKAKI, S. KOMINAMI, S. TAKEMORI, H. OHKAWA, M. AKIYOSHI- SHIBATA, Y. YABUSAKI

433 Overexpression of yeast cytochrome b5 gene can supress ketoconazole hypersensitivity of a NADPH-P450 reductase deficient strain. G. TRUAN, J.-C. EPINAT, C. ROUGEULLE, C. CULLIN, D. POMPON

437 Structure-function interrelationships in mitochondrial and microsomal cytochrome P-450-dependent monooxygenases. S.A. USANOV, M. IWASAKI, M. NEGISHI

XVII 441 Direct evidence of the electron releasing character of the cysteinate proximal ligand of cytochrome P450 from X-ray absorption near edge- spectroscopy. J.H. DAWSON, H.I. LIU, M. SONO, S. KADKHODAYAN, B. HEDMAN, K.O. HODGSON

445 Electron transfer in cytochrome P450 containing semi-artificial enzymes. V.Y. UVAROV, V.V. SHUMYANTSEVA, E.A. BYKHOVSKAYA, L.N. KOLYADA, A.I. ARCHAKOV

451 Segment directed mutagenesis of human cytochrome P450 1A2 by PCR ana effect on the catalytic activity and substrate selectivity R. LAINE, P. URBAN, D. POMPON

455 Specific inhibition of the last steps of the aldosterone biosynthesis by 18-vinylprogesterone in bovine adrenocortical cells. G. DEFAYE, A. PIFFETEAU, C. DELORME, A. MARQUET

459 Mechanism based inactivation of nitric oxide synthase, a P450 like enzyme, by xenobiotics. Y. OSAWA, J.C. DAVILA, C.A. MEYER, M. NAKATSUKA

463 Molecular recognition in cytochrome P450: control of uncoupling reactions via site-directed mutagenesis. P.J. LOIDA, S.G. SLIGAR

467 Metabolism of two dopaminergic ergot derivatives in genetically engineered V79-cells expressing CYP450-enzymes. H. GIESCHEN, M. HILDEBRAND, B. SALOMON

471 Mutants affecting substrate recognition and substrate binding in P450BM-P. S. GRAHAM-LORENCE, D. SANDERS, J.A. PETERSON

CYTOCHROME P450. VII BIOCHEMISTRY, BIOPHYSICS AND MOLECULAR BIOLOGY

A77 The use of synthetic peptides for the investigation of components interaction in monooxygenase rabbit liver system. A.M. KRITSKY, I.P. KANAEVA, D.R. DAVYDOV, N V STEPANOVA, G.I. BACHMANOVA

481 Multiple forms of NADPH-cytochrome P450 reductase in higher plants A. LESOT, C. BEGUE-KIRN, M.P. HASENFRATZ, F. DURST, I. BENVENISTE

XVIII 485 Strain- and tissue-specific expression of rat CYP2B. A.Y. GRISHANOVA, L GULYAEVA, E.V. PETCHKOVSKI, V.V. LYAKHOVICH

489 The studies of cytochrome P450scc in liposomes by means of limited trypsinolysis. A.V. KRIVOSHEEV, O.N. MURASHKO, S.A. USANOV

493 Computer modeling of cytochrome P450cam and b5 interaction. AS. IVANOV, VS. SKVORTSOV, Y.A. LYULKIN, A.B. RUMYANTSEV

497 Wild mice as bioindicators for pollution monitoring. A. BHATIA, K. MAZZUCCO

503 Expression of functional human microsomal epoxide hydrolase in Escheri- cnia coli A. GAEDIGK, H. NAKAMURA, D.M. GRANT

507 Regulation of CYP2B gene expression in the intestinal mucosa. A.P. ELIA, E.A. SHEPHARD, I.R. PHILLIPS

511 Clofibrate decreases CYP2A5 in male DBA/2N mice. A. KOJO, S. LAITINEN, P. PELLINEN, R. JUVONEN, H. RAUNIO, O. PELKONEN, M. PASANEN

515 Exchange of N- or C- terminal segments between human P4501A1 and 1A2 leads respectively to high stability and high activity chimeras. A. BELLAMINE, D. POMPON

519 Assessment of CYP2A6 and CYP3A4 activities in vivo in different diseases in man. A. RAUTIO, E. SALMELA, P. ARVELA, O. PELKONEN, E.A. SOTAN1EMI

523 Putative active site model for CYP2C9 (tolbutamide hydroxylase). B.C. JONES, G. HAWKSWORTH, V. HORNE, A. NEWLANDS, M. TUTE, D.A. SMITH

527 Expression of a bovine P450c17 cDNA in the yeast Saccharomyces cerevisiae. B. DUMAS, G. CAUET, E. DEGRYSE, R. SPAGNOLI, T. ACHSTETTER

531 Conformational dynamics of cytochrome P450cam as monitored by photoacoustic calorimetry. C. Dl PRIMO, G. HUI BON HOA, E. DEPREZ, P. DOUZOU, S.G. SUGAR

535 The molecular basis of aromatase deficiency in an adult female due to mutations in the CYP19 gene. C.R. FISHER, Y. ITO, FA. CONTE, M.M. GRUMBACH, E.R. SIMPSON

XIX 539 The loss of cytochromes P450 (CYPs) in rat liver cell culture is triggered during hepatocyte isolation and again during the first 4 hours of culture. C.R.W. PADGHAM, X.-J. WANG, AJ. PAINE

543 Conformationa! states and substates of cytochrome P450cam - insight in protein dynamics and folding. C. JUNG, W. PFEIL, K. KOPKE, H. SCHULZE, O. RISTAU

547 Hepatic cytochrome P450 profile in BB rats with spontaneous insulin- dependent diabetes mellitus. C.R. BARNETT, P.R. FLATT, AJ. BONE, C. IONNIDES

551 2,3,7,8-tetrachlorodibenzo-p-dioxin versus 3-methylcholanthrene. Ah receptor binding, transformation and induction of CYP1 Al. D.S. RIDDICK, PA. HARPER, A.B. OKEY

555 Reconstitution of cytochrome P450scc by octylglucoside dialysis/adsorption into (large) unilamellar phospholipid vesicle . Structural and functional characterization. D. SCHWARZ, A. CHERNOGOLOV, K. GAST, W. RICHTER

559 Pressure-induced transitions in cytochrome P450 IIB4 (LM2): evidence of the conformational inhomogeneity in the oligomers in solution and in proteoliposomes. D.R. DAVYDOV, G. HUI BON HOA

563 The effect of phenobarbitone and (3-naphfhoflavone on selected biochemi- cal liver parameters following subchronic administration to female beagle dogs. E. MOLITOR, H. THOMAS, J. WEYMANN, F. WAECHTER

567 1, 3-butadiene exposure of rats: hemoglobin adducts of 1,2-epoxybutene and cytochrome P450 related changes in styrene metabolism. E. ELOVAARA, S. OSTERMAN-GOLKAR, T. NAKAJIMA, H.V. GELBOIN, V. RIIHIMAKI, M. SORSA

571 Tritium planigraphy study on cytochrome P450 2B4 structure. E.V. APLETALINA, V. YU. UVAROV, O.M. IPATOVA

575 Carcinogenic activation of cooked food heterocyclic amines by cytochrome P450 1A2. A theoretical study. F. SANZ, J.J. LOZANO, E. LOPEZ-DE-BRINAS, R. DE-LA-TORRE, F. MANAUT

579 Three-dimensional structure of active-site of cytochrome P450 1A2. F. MANAUT, E. LOPEZ-DE-BRINAS, JJ. LOZANO, F. SANZ

XX 583 Expression of a bovine P450np cDNA in the yeast Saccharomyces cerevisiae. G. CAUET, B. DUMAS, E. DEGRYSE, R. SPAGNOLI, T. ACHSTETTER

587 Induction by phenobarbital of CYP2B gene expression in primary rat hepafocytes and in rat hepatoma cell line. G. CIARAMELLA, M. EDWARDS, E.A. SHEPHARD, I.R. PHILLIPS

591 Molecular cloning of cDNA for a renal 27-hydroxylating cytochrome P450. H. POSTLIND

595 Low temperature behaviour of the high-spin/low-spin equilibrium of cytochrome P450 : the role of the cooling rate and temperature induced changes of the protonic activity. H. SCHULZE, O. RISTAU, C. JUNG

599 Induction of cytochrome P450IA1 mRNA in aryl hydrocarbon hydroxylase- deficient mutants of mouse hepatoma line, Hepa-1. H. KIKUCHI, M. USUDA, I. SAGAMI, S. IKAWA, M. WATANABE

603 Antigenic determinants of cytochrome P450 superfamily and their classification. I.R. DEDINSKY, S.A. KOZIN, A.I. ARCHAKOV

611 Vitamin D3 hydroxylases in human skin. I. SCHUSTER, H. EGGER, G. HERZIG, G. VORISEK

615 Two cytochrome P450 aldosterone synthase mRNAs are present in the hamster adrenal. J.-G. LeHOUX, H. BERNARD, L DUCHARME, A. LEFEBVRE, J. LeHOUX, S. VERONNEAU

619 Purification of the insect P450 enzyme, ecdysone 20-hydroxylase, from the migratory locust, Locusta migratoria, by a new affinity method. J. WINTER, H. KAYSER

623 Effect of carrageenan-induced granuloma on the apoprotein content and activities of cytochrome P450 isozymes in liver and nasal mucosa in rats. J. MUNTANE, V. LONGO, M.T. MITJAVILA, P.G. GERVASI, M. INGELMAN-SUNDBERG

627 Interaction of ethanol and type I binding substrate n-heptane with liver cytochrome P450 from male rats. J.S. RAKOTO, M.M. SZUTOWSKI

XXI 631 Coumarin and methoxsalen metabolism by CYP2A6 and CYP2A-5 isoforms in man and mouse. J. MAENPAA, R. JUVONEN, H. RAUNIO, A. RAUTIO, O. PELKONEN

635 Accelerated caffeine metabolism after omeprazole treatment: measure- ments in breath, plasma and urine. K.L. ROST, I. ROOTS

639 The effect of dexamethasone and phenobarbital coadministration on the activity of rat liver P450 system. K. MONOSTORY, L VERECZKEY

643 Polymerase chain reaction mediated detection of cytochrome P450 gene in the yeast Candida apicola. K. LOTTERMOSER, O. ASPERGER, W.-H. SCHUNCK

647 Chicken cytochrome P450]7a: cloning of active type E2 and mutated type A2 defective in 17,20-lyase activity. K. NISHIMORI, H. IKUSHIMA, S. MIZUNO.

651 Expression of aromatase cytochrome P450 in choliocarcinoma cells. K. YAMADA, S. KATOH, N. HARADA, Y. TAKAGI

655 Immortalization of hepatocytes via a transgenic approach. K. KRAMER, G. CIARAMELLA, M. EDWARDS, E.A. SHEPHARD, I.R. PHILLIPS

659 Analyses of promoter regions of rat CYP1 IB genes involved in mineralo- and glucocorticoid syntheses. K. MUKAI, H. SHIMADA, Y. ISHIMURA

663 Regulatory proteins involved in the tissue-specific expression and induction ofaCYP2B2gene. L.M. FERNANDEZ, LA. FORREST, A. SHERVINGTON, E.A. SHEPHARD, I.R. PHILLIPS

667 Breast cancer aromafase: identification and expression of cytochrome P450 aromatase mRNA in T47D breast cancer cells. L. TAN, S.I. SADEKOVA, T.Y.K. CHOW

671 Spectral map analysis of cytochrome P450 isoenzymes. L.M.H. KOYMANS, H. MOEREELS, P.J. LEWI, RAJ. JANSSEN

677 Oxidative dealkylation of N,N-dialkylamides. L. CONSTANTINO, J. ILEY

681 Influence of isoamyl alcohol and ethanol on the oesophageal and hepatic cytochrome P450 metabolism of nitrosamines and their carcinogenicity. L.F. RIBEIRO PINTO, P.F. SWANN

XXII 685 Regulation of the rat liver and lung CYP1A expression by different inducers. L.F. GULYAEVA, A.Y. GRISHANOVA, E.V. PETCHKOVSKI, V.V. LYAKHOVICH

689 Expression study of CYP genes in drosophila strains resistant or sensitive to insecticides. M. AMICHOT, A. BRUN, A. CUANY, C. HELVIG, J.P. SALAUN, F. DURST, J.B. BERGE

693 Metabolism of selected sex steroids by rat CYP1A1, 1A2 and 2B1 expressed in V79 cell lines. M. HILDEBRAND, H. GIESCHEN, B. SALOMON

697 Thiophene derivatives as new mechanism-based inhibitors of cytochromes P450: inactivation of yeast expressed human liver cytochrome P450 2C9 by tienilic acid. M.P. LOPEZ-GARCIA, P.M. DANSETTE, D. MANSUY

701 Cholesterol-binding region of cytochrome P450scc (P-450XIA1): identification and amino acid sequence of the cholesterol binding domain. M. TSUJITA, Y. ICHIKAWA

705 Inhibition of cytochrome P450 enzyme activity using specific inhibitory antibodies. M. HATCHER, R. BROWN, M.J. O'SULLIVAN, S. SWINBURNE

709 Mammalian cell lines stably expressing bovine adrenal 11 p-hydroxylase cDNA. M. HUSEMANN, T PETRI

713 Expression of cDNAs encoding human and marmoset CYP2As. M. NANJI, P. CLAIR, I.R. PHILLIPS, E.A. SHEPHARD

717 Localization and distribution of CYP2B1 in the rat lung by immunocytoche- mistry and by in situ hybridization. M.H. FIGUEIREDO, V. RIBEIRO, D. HENRIQUE, M.C. LECHNER, V. BAIROS

721 Site directed mutagenesis on bovine adrenodoxin to target amino acids involved in electron transfer and binding to adrenodoxin reductase and cytochrome P450 . M.-F. PALIN, J. SYGUSCH, J.-G. LEHOUX

725 Cytochrome P450 obtusifoliol 14a-methyl demerhylase from Zea mays: enzymology and inhibition. M. TATON, F. SALMON, A. RAHIER

XXIII 729 Mechanism of 9-hydroxy ellipticine induced inhibition of hepatic aryl hydrocarbon hydroxylase. M.J. OLNES, P.B. DePETRILLO, R.N. KURL

733 Induction of rat liver cytochrome P450 3A1 by metyrapone. M.C. WRIGHT, AJ. PAINE

737 Long-term preservation and induction of cytochromes P450 in co-cultured rat nepatocytes. M. AKRAWI, V. ROGIERS, A. VERCRUYSSE, I.R. PHILLIPS, E.A. SHEPHARD

741 Development and prevalidation of an Escherichia coli tester strain for genotoxins. M. KRANENDONK, M. RUAS, A. LAIRES, J. RUEFF

745 Coumarin 7-hydroxylation (CYP2A6) polymorphism in a Turkish population. M. ISCAN, H. ROSTAMI, M. ISCAN, T. GURAY, A. RAUTIO, O. PELKONEN

749 Exon-7 point mutation (m2; 4889A->G) in human CYP1A1 gene as susceptibility factor for lung cancer. N. DRAKOULIS, I. CASCORBI, J. BROCKMOLLER, C.R. GROSS, I. ROOTS

753 A role for Asp251 in the activation of oxygen by cytochrome P450cam. N.C. GERBER, S.G. SUGAR

757 Activation and regulation of aromatic hydrocarbon-inducible Cyplal and C/pl a2 gene expression in mouse hepatocytes in primary culture. N. NEMOTO, J. SAKURAI

761 Species differences in the in vitro metabolism of probe substrates for CYP2 enzymes. O.M. CORCORAN, R. HYLAND, B.C. JONES, D.A. SMITH

765 Resonance raman spectra of NADPH cytochrome P450 reductase and its complex with cytochrome P450 2B4. O. ALEXANDROVA, Y. IVANOV, V. UVAROV

769 Effects of acute and chronic acetone administration on cytochrome P450 2E1 mRNA in murine liver using in situ hybridization. P.G. FORKERT, A.C. JACKSON, S. CHEN, S.P. TAM

773 Downregulation of the Ah receptor following 2, 3, 7, 8-tetrachlorodibenzo- p-dioxin (TCDD) treatment in Hepa-1 cells in culture. P.A. HARPER, J.V GIANNONE, M.R. PROBST, A.B. OKEY

777 Lidocaine metabolism as a liver function test. P. ARVELA, A. RAUTIO, E.A. SOTANIEMI XXIV 781 Formation of cytochrome P450 metabolite complexes: isozyme specificity and use for isozyme quantitation. PH. ROOS, G. GUNTHER, W.G. HANSTEIN

785 Risk assessment and bioavailability for mammals of soil-bound polycyclic aromatic hydrocarbons. P.H. ROOS, W.G. HANSTEIN, D. STROTKAMP, M. VAN AFFERDEN, D. TAPPE

789 Expression of components of the cytochrome P450 mediated mono-oxyge- nase system using recombinant baculoviruses. P. CLAIR, E.A. SHEPHARD, I.R. PHILLIPS

793 Advantages of the human over yeast NADPH-P450 reductase on suppor- ting human P450 activities in yeast. P. URBAN, A. PERRET, G. TRUAN, D. POMPON

797 Inducing effect of porphyrinogenic agents on mouse liver Cyp2a-5 expression. P. SALONPAA, K. KRAUSE, O. PELKONEN, H. RAUNIO

801 Function of residue-365 in mouse P4502A5 (P450coh): site directed mutagenesis, spectral and enzymatic properties. R.O. JUVONEN, M. IWASAKI, M. NEGISHI

805 Looking for the gene encoding the fungal cytochrome P450 involved in 11 p-hydroxylation of steroids: application of PCR techniques. R. KOMEL, D. ROZMAN, M. VITAS, K. DROBIC, S.L. KELLY

809 Interaction of verapamil and cimetidine in rat liver microsomes. R. WACKE, U. FISCHER, J. AHREND, B. DREWELOW

813 Stopped flow kinetics under high pressure: an approach to explore the transition state of haemoproteins in elementary reactions. R. LANGE, I. HEIBER-LANGER, N. BEC, C. BALNY

817 A three-dimensional model of P450arom using P450BM-P as a template. S. GRAHAM-LORENCE, J.A. PETERSON, E.R. SIMPSON

821 Ortho- and para-hydroxylation of pentachlorophenol in aquatic plants: possible involvement of cytochrome P450. S. ROY, O. HANNINEN

825 Cytochrome P450 1 Al expression during the differentiation process in the Caco-2 cell line. S. CHARRASSE, I. FABRE, M. DAUJAT, P. MAUREL, C. LARROQUE

XXV 829 Substrate-regulated, cAMP-dependent phosphorylation of cytochrome P450 3A1. S. MKRTCHIAN, E. ELIASSON, J.R. HALPERT, M. INGELMAN-SUNDBERG

833 Growth hormone regiospecificically represses the expression of CYP2B1/2 and CYP3A in liver. T. OINONEN, K.O. LINDROS

837 Developmentally programmed changes in CYP3A1 induction by dexamethasone in male rat liver. T. PEREIRA, M.C. LECHNER

841 Different mechanisms of regioselection of fatty acid hydroxylation by two laurate (tD-1) - hydroxylating P450s. T. FUKUDA, Y. IMAI, M. KOMORI, M. NAKAMURA, E. KUSUNOSE, K. SATOUCHI, M. KUSUNOSE

845 Use of the paraxathine/caffeine ratio in plasma and in saliva for CYP1A2 phenotyping. U. FUHR, K.L ROST, R. ENGELHARDT, A. HORST STAIB

849 Human CYP1A2 activity: relationship between caffeine clearance in vivo and its 3-demethylation in vitro. U. FUHR, R. ENGELHARDT, M. SACHS, K.L. ROST, P. SCHYMANSKY, C. HUSCHKA, D. LIERMANN, H. WISSING, A. HORST STAIB

853 Prediction and experimental confirmation of the cytochromes b5 and P450 peptide mapping. V. ZGODA, D. PROSCHLYAKOV, O. IPATOVA, V. PROSOROVSKY, G. BACHMANOVA

857 Modulation of CYP3A1 expression by heme in transfected COS-1 cells. V. RIBEIRO, M.C. LECHNER

861 Limited proteolysis of cytochrome P450c21 from bovine adrenal cortex microsomes. V.M. GUZOV, I.N. ZELKO, S.A. BYLINSKAYA, S.A. USANOV

865 Interaction of FITC with P450s' N-terminus VV SHUMYANTSEVA, G.P. KUZNETSOVA, V.Y. UVAROV, A.I. ARCHA KOV

869 Structural requirements for ferredoxin associated electron transfer evalua- ted by analysis of Tyr-82 and His-56 bovine adrenodoxin mutants. V. BECKERT, R. DETTMER, R. BERNHARDT

XXVI 873 Nonchemical induction of rat liver CYP1 Al. V.V. LYAKHOVICH, A.Y. GRISHANOVA, O.A. GROMOVA, L.F. GULYAEVA

877 Inhibition of cyclosporine metabolism in mouse and human microsomes after cytochrome P450 inactivation by Cannabidiol. W JAEGER, LM. BORNHEIM, M.A. CORREIA, L.Z. BENET

881 Ethinyl estradiol-mediated induction of a cyclosporin A metabolizing 2C6 isozyme in rats. W. JAEGER, M.A. CORREIA, LM. BORNHEIM, L.Z. BENET

885 Heterologous expression and structure-function analysis of CYP2A10 and CYP2A11, which differ in only eight amino acids but have strikingly different activities toward testosterone and coumarin. X. DING, H.M. PENG, MJ. COON

889 Dynamic topology and electron transfer interactions of microsomal cytochrome P450 in liver and adrenal cortex: protein rotation study. Y. OHTA, M. YAMADA, S. KAWATO

893 Diverse functions of aromatase cytochrome P450: catecholestrogen synthe- sis, cocaine N-demethylation, and other selective drug metabolisms. Y. OSAWA, T. HIGASHIYAMA, C. YARBOROUGH

897 Computer modeling of cytochromes P450cam interaction with camphor and its derivatives by Monte Carlo method. Y.A. LYULKIN, A.S. IVANOV, VS. SKVORTSOV, A.B. RUMYANTSEV

899 Inhibition of cytochrome P450 enzymes by cytokines in human hepatocyte cultures. Z.A. RAZZAK, L. CORCOS, A. GUILLOUZO

WILL I CYTOCHROME P450'S : AGENDA FOR ACTION, ADAPTATION VHI[ AND APPLICATION

905 The P450s: agenda for action, adaptation, and application. R.W ESTABROOK

XXVII