The Cellular Response to the Genotoxic Insult: The Question of Threshold for Genotoxic Carcinogens (Issues in Toxicology)

ISBN 10: 1849731772 / ISBN 13: 9781849731775

Editore: Royal Society of Chemistry, 2012

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Codice articolo 183522269

Dati bibliografici

• Titolo: The Cellular Response to the Genotoxic Insult: The Question of Threshold for Genotoxic Carcinogens (Issues in Toxicology)
• Editore: Royal Society of Chemistry
• Data di pubblicazione: 2012
• Lingua: Inglese
• ISBN 10: 1849731772
• ISBN 13: 9781849731775
• Rilegatura: Rilegato
• Condizione: New

Descrizione articolo

Riassunto

Although the cellular defence mechanisms are increasingly understood, the critical and rate limiting parameters and their dose-response to the insulting agent need to be evaluated. In this book the different cellular defence mechanisms and their regulation are described. Understanding the protective mechanisms by which the cell responds to a genotoxic impact to protect integrity of the genomes will permit the evaluation of whether the assumption of a threshold for genotoxic carcinogens at low dose exposure is justified. Besides its scientific value, this dispute is of regulatory importance since it may result in a scientifically defendable threshold concept for genotoxic carcinogens, will allow identification of a NOEL and by that to propose health based exposure limits - even for genotoxic carcinogens. Genotoxic carcinogens can lead to DNA mutations with the potential to cause cancer. Typically, a series of mutation events are needed before malignancy occurs so a single, small exposure may not result in disease. Also, cells have an armoury of defence mechanisms which, to a degree, counter the effects of mutagens. Distinguishing the point at which exposure to a carcinogen increases mutation rates beyond the background level is challenging. In fact, there is now general agreement that, for genotoxic carcinogens, no specific threshold can be identified. However, NOAELs (No Observed Adverse Effect Levels) may be used in the process of establishing a dose-response relationship. These denote the level of exposure at which there is no significant increase in adverse effects in the exposed population when compared to an appropriate control. Such a scientifically defendable threshold allows us to propose health based exposure limits for genotoxic carcinogens. This book describes the various cellular defence mechanisms individually and explains how they are regulated. The processes covered include metabolic inactivation, epigenetic regulation, scavenging mechanisms, DNA-repair and apoptosis. It also considers dose-dependent threshold mechanisms of carcinogenesis and the rate limiting parameters. Aimed at graduate level and above, the book discusses the consequences of genotoxic evaluation and urges readers to question the idea that even low exposures present a cancer risk.

Informazioni sull?autore

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.