Über die Autorin bzw. den Autor

Helmut Greim is a toxicologist and former chair of the Institute of Toxicology and Environmental Hygiene at the Technical University of Munich, Germany. His research experience is drug metabolism, toxicokinetics, mechanisms of carcinogenic agents, in vitro test systems. He has been member or chair of numerous national and international scientific committees. In 1996 he received the Arnold Lehman Award of SOT and in 2001 the Herbert Stockinger Award of the American Conference of Governmental Industrial Hygienists. At present he chairs the Scientific Committee on Health and Environmental Risks of the DG SANCO, Brussels, is member of the Scientific Committee on Occupational Exposure Limits of DG EMPLOYMENT, Luxembourg and member of the Risk Assessment Committee of the European Chemicals Agency in Helsinki, Finland. Dr. Albertini is currently Research Professor of Pathology at the University of Vermont (USA). He retired from the Department of Medicine at that University in 2000 and is now an Emeritus Professor of Medicine. He received the M.D. degree in 1963 and a Ph.D. in Medical Genetics in 1972, both from the University of Wisconsin, Madison (USA). Dr. Albertini joined the Department of Medicine at the University of Vermont that same year, becoming full Professor in 1979. He was clinically active in the areas of oncology, hematology and AIDS for many years and served as Director of the Vermont Cancer Center from 1993 to 1995. Dr. Albertini's fundamental research has been and remains in the area of mutagenesis and the relationship of somatic mutations to cancer. In the past, Dr. Albertini served as President of the Environmental Mutagen Society and as editor-in-chief of Environmental and Molecular Mutagenesis.

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The Cellular Response to the Genotoxic Agent: The Question of Threshold for Genotoxic Carcinogens describes the different cellular defence mechanisms and their regulation. On the basis of this the plausibility of a dose dependent threshold mechanisms of genotoxic/ mutagenic carcinogens and their rate limiting parameters are discussed and it is concluded that low exposures to genotoxic/mutagenic agents present no cancer risk. The book begins with a detailed introduction by the editors explaining the rationale for thresholds for genotoxic carcinogens. The contents are then broken down into five main parts. The first part discusses threshold effects observed in experimental studies and includes chapters on mechanisms responsible for the chromosome and gene mutations driving carcinogenesis and implications for dose-response characteristics of mutagenic carcinogens; the dose-effect relationships of DNA-reactive liver carcinogens and DNA alkylation and repair after EEMS exposure. Part two discusses metabolic inactivation of genotoxic reactants and includes chapters on enzymatic detoxification of endogenously produced DNA-reactive intermediates maintaining cellular homeostasis and detoxifying enzymes and anti-oxygen defense mechanisms. Part three focuses on DNA repair; the plasticity of DNA damage response during cell differentiation and tumor suppressor protein-mediated regulation of base excision repair in response to DNA damage. Finally, the role of apoptosis, necrosis and epigenetic mechanisms in the elimination of damaged cells is discussed. The book will be essential reading for postgraduate students and scientific researchers working in environmental health, medicine, genetic toxicology and risk assessment.

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The Cellular Response to the Genotoxic Insult

The Question of Threshold for Genotoxic Carcinogens

The Royal Society of Chemistry

Contents

Introduction and Conclusion: The Rationale for Thresholds for Genotoxic Carcinogens Helmut Greim and Richard J. Albertini, 
1. Threshold Effects Observed in Experimental Studies, 
2. Metabolic Inactivation of Genotoxic Reactants, 
3. DNA Repair, 
4. Apoptosis, 
5. Epigenetic Mechanisms, 
Subject Index,