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EXS 99 Molecular, Clinical and Environmental Toxicology Volume 1: Molecular Toxicology Edited by Andreas Luch Birkhäuser Verlag Basel · Boston · Berlin Editor Andreas Luch Federal Institute for Risk Assessment Thielallee 88-92 14195 Berlin Germany Library of Congress Control Number: 2008938291 Bibliographic information published by Die Deutsche Bibliothek Die Deutsche Bibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data is available in the Internet at http://dnb.ddb.de ISBN 978-3-7643-8335-0 Birkhäuser Verlag AG, Basel – Boston – Berlin This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, re-use of illustrations, recitation, broad- casting, reproduction on microfilms or in other ways, and storage in data banks. For any kind of use, permission of the copyright owner must be obtained. The publisher and editor can give no guarantee for the information on drug dosage and administration contained in this publication. The respective user must check its accuracy by consulting other sources of reference in each individual case. The use of registered names, trademarks etc. in this publication, even if not identified as such, does not imply that they are exempt from the relevant protective laws and regulations or free for general use. © 2009 Birkhäuser Verlag AG Basel – Boston – Berlin P.O. Box 133, CH-4010 Basel, Switzerland Part of Springer Science+Business Media Printed on acid-free paper produced from chlorine-free pulp. TFC ∞ Cover illustration: with friendly permission of Andreas Luch Cover design: Benjamin Blankenburg, Basel, Switzerland Printed in Germany ISBN 978-3-7643-8335-0 e-ISBN 978-3-7643-8336-7 987654321 www. birkhauser.ch V Contents List of contributors . VII Preface . XI Antoinette N. Hayes and Steven G. Gilbert Historical milestones and discoveries that shaped the toxicology sciences . 1 David Kim and Leena A. Nylander-French Physiologically based toxicokinetic models and their application in human exposure and internal dose assessment . 37 Wolfgang Dekant The role of biotransformation and bioactivation in toxicity . 57 David H. Phillips and Volker M. Arlt Genotoxicity: damage to DNA and its consequences . 87 Ulrike Camenisch and Hanspeter Naegeli Role of DNA repair in the protection against genotoxic stress . 111 Andreas Luch On the impact of the molecule structure in chemical carcinogenesis . 151 Johan Högberg, Ilona Silins and Ulla Stenius Chemical induced alterations in p53 signaling . 181 Roberto Sánchez-Olea Mónica R. Calera and Alexei Degterev Molecular pathways involved in cell death after chemically induced DNA damage . 209 Ci Ma, Jennifer L. Marlowe and Alvaro Puga The aryl hydrocarbon receptor at the crossroads of multiple signaling pathways . 231 Jennifer Marlowe, Soon-Siong Teo, Salah-Dine Chibout, François Pognan and Jonathan Moggs Mapping the epigenome – impact for toxicology . 259 VI Contents Joëlle Rüegg, Pauliina Penttinen-Damdimopoulou, Sari Mäkelä, Ingemar Pongratz and Jan-Åke Gustafsson Receptors mediating toxicity and their involvement in endocrine disruption . 289 Tong Zhou, Jeff Chou, Paul B. Watkins and William K. Kaufmann Toxicogenomics: transcription profiling for toxicology assessment . 325 B. Alex Merrick and Frank A. Witzmann The role of toxicoproteomics in assessing organ specific toxicity . 367 Willem G. E. J. Schoonen, Walter M. A. Westerink and G. Jean Horbach High-throughput screening for analysis of in vitro toxicity . 401 Glossary ................................................. 453 Index .................................................... 461 VII List of contributors Volker M. Arlt, Institute of Cancer Research, Section of Molecular Carcinogenesis, Brookes Lawley Building, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom; e-mail: [email protected] Mónica R. Calera, Instituto de Física, Universidad Autónoma de San Luis Potosí, México; e-mail: [email protected] Ulrike Camenisch, Institute of Pharmacology and Toxicology, University of Zürich-Vetsuisse, Winterthurerstrasse 260, 8057 Zürich, Switzerland; e-mail: [email protected] Salah-Dine Chibout, Investigative Toxicology, Preclinical Safety, Novartis Pharma AG, 4002 Basel, Switzerland; e-mail: salahdine.chibout@ novartis.com Jeff Chou, Microarray Group, National Institute for Environmental Health Sciences, Research Triangle Park, NC, USA; e-mail: [email protected] Alexei Degterev, Department of Biochemistry, Tufts University School of Medicine, Boston, MA 02111, USA; e-mail: [email protected] Wolfgang Dekant, Department of Toxicology, University of Würzburg, Versbacher Straße 9, 97078 Würzburg, Germany; e-mail: [email protected] wuerzburg.de Steven G. Gilbert, Institute of Neurotoxicology & Neurological Disorders, 8232 14th Ave NE, Seattle, WA 98115, USA; e-mail: [email protected] Jan-Åke Gustafsson, Department of Biosciences and Nutrition, Karolinska Institutet, Hälsovägen 7, 14157 Huddinge, Sweden; e-mail: jan-ake. [email protected] Antoinette N. Hayes, Wyeth Research, One Burtt Road, Andover, MA 01810, USA; e-mail: [email protected] Johan Högberg, Institute of Environmental Medicine, Karolinska Institutet, 17177 Stockholm, Sweden; e-mail: [email protected] G. Jean Horbach, Department of Pharmacology, NV Organon (Schering- Plough), Molenstraat 110, 5340 BH Oss, The Netherlands; e-mail: [email protected] William K. Kaufmann, Department of Pathology and Laboratory Medicine, Center for Environmental Health and Susceptibility, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; e-mail: [email protected] David Kim, Department of Environmental Health, School of Public Health, Harvard University, 401 Park Drive, Boston, MA 02215, USA; e-mail: [email protected] Andreas Luch, Department for Product Safety and ZEBET, Federal Institute VIII List of contributors for Risk Assessment, Thielallee 88-92, 14195 Berlin, Germany; e-mail: [email protected] Ci Ma, Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati College of Medicine, 3223 Eden Ave, Cincinnati, OH 45220, USA; e-mail: [email protected] Sari Mäkelä, Functional Foods Forum & The Department of Biochemistry and Food Chemistry, University of Turku, Finland; e-mail: [email protected] Jennifer L. Marlowe, Investigative Toxicology, Preclinical Safety, Novartis Pharma AG, 4132 Muttenz, Switzerland; e-mail: jennifer.marlowe@ novartis.com B. Alex Merrick, Laboratory of Respiratory Biology, National Institute for Environmental Health Sciences (NIEHS), 111 Alexander Drive, Research Triangle Park, Durham, NC 27709, USA; e-mail: [email protected] Jonathan Moggs, Investigative Toxicology, Preclinical Safety, Novartis Pharma AG, 4132 Muttenz, Switzerland; e-mail: Jonathan.Moggs@ novartis.com Hanspeter Naegeli, Institute of Pharmacology and Toxicology, University of Zürich-Vetsuisse, Winterthurerstrasse 260, 8057 Zürich, Switzerland; e-mail: [email protected] Leena A. Nylander-French, Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; e-mail: [email protected] Pauliina Penttinen-Damdimopoulou, Functional Foods Forum & The Department of Biochemistry and Food Chemistry, University of Turku, Finland; e-mail: [email protected] David H. Phillips, Institute of Cancer Research, Section of Molecular Carcinogenesis, Brookes Lawley Building, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom; e-mail: [email protected] François Pognan, Investigative Toxicology, Preclinical Safety, Novartis Pharma AG, 4132 Muttenz, Switzerland; e-mail: francoise.pognan@ novartis.com Alvaro Puga, Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati College of Medicine, 3223 Eden Ave, Cincinnati, OH 45220, USA; e-mail: [email protected] Ingemar Pongratz, Department of Biosciences and Nutrition, Karolinska Institutet, Hälsovägen 7, 14157 Huddinge, Sweden; e-mail: ingemar. [email protected] Joëlle Rüegg, Department of Biosciences and Nutrition, Karolinska Institutet, Hälsovägen 7, 14157 Huddinge, Sweden; e-mail: [email protected] Roberto Sánchez-Olea, Instituto de Física, Universidad Autónoma de San Luis Potosí, México; e-mail: [email protected] Willem G.E.J. Schoonen, Department of Pharmacology, NV Organon (Schering-Plough), Molenstraat 110, 5340 BH Oss, The Netherlands; e-mail: [email protected] Ilona Silins, Institute of Environmental Medicine, Karolinska Institutet, 17177 List of contributors IX Stockholm, Sweden; e-mail: [email protected] Ulla Stenius, Institute of Environmental Medicine, Karolinska Institutet, 17177 Stockholm, Sweden; e-mail: [email protected] Soon-Siong Teo, Investigative Toxicology, Preclinical Safety, Novartis Pharma AG, 4132 Muttenz, Switzerland; e-mail: [email protected] Paul B. Watkins, Center for Drug Safety Sciences, The Hamner Institutes for Health Sciences, University of North Carolina at Chapel Hill, Research Triangle Park, NC, USA; e-mail: [email protected] Walter M.A. Westerink, Department of Pharmacology, NV Organon (Schering-Plough), Molenstraat 110, 5340 BH Oss, The Netherlands; e-mail: [email protected] Frank A. Witzmann, Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA; e-mail: [email protected] Tong Zhou, Center for Drug Safety Sciences,
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