Catalogue


The cellular response to the genotoxic insult [electronic resource] : the question of threshold for genotoxic carcinogens /
edited by Helmut Greim, Richard J. Albertini.
imprint
Cambridge, UK : RSC Publishing, c2012.
description
xiv, 319 p. : ill. ; 25 cm.
ISBN
1849731772 (cased), 9781849731775 (cased)
format(s)
Book
More Details
imprint
Cambridge, UK : RSC Publishing, c2012.
isbn
1849731772 (cased)
9781849731775 (cased)
restrictions
Licensed for access by U. of T. users.
catalogue key
12580552
 
Includes bibliographical references and index.
A Look Inside
Reviews
Review Quotes
"This book will, therefore, make excellent and stimula ting reading for all toxicologists (from the student to the most senior toxicologist} in academia, industry and government as well as scienlists responsible for health risk assessment. It urges readers to accept scientifically based thresholds not only for non-genotoxic (epigenetic) carcinogens but also - and more importantly - for genotoxic carcinogens. It is highly recommended!"
To find out how to look for other reviews, please see our guides to finding book reviews in the Sciences or Social Sciences and Humanities.
Summaries
Back Cover Copy
So far, there is general agreement that for genotoxic carcinogens no threshold can be identified. However, there are examples that the shape of the dose-responses of DNA adducts and mutations differ and it is also evident that the dose response for mutations will reach the background mutation frequency. This implies, that at low doses the mutation rate induced by a genotoxicity/mutagenicity carcinogen becomes indistinguishable from the background. Moreover, the array of cellular defence mechanisms such as metabolic inactivation, DNA-repair and apoptosis makes it unlikely that a single event overcomes these barriers to cancer. This confirms the experimental evidence of NOELs for carcinogenic and mutagenic effects in repeated dose studies in animals. In this book the different cellular defence mechanisms and their regulation are described. On the basis of this the plausibility of a dose dependent threshold mechanisms of genotoxicity/mutagenicity carcinogens and their rate limiting parameters are discussed and it is concluded that the notion that even low exposures to genotoxicity/mutagenicity agents present a cancer risk is to be questioned.
Bowker Data Service Summary
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 text, the different celular defence mechanisms and their regulation are described.
Description for Bookstore
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.
Description for Bookstore
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.
Back Cover Copy
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 even low exposures to genotoxic/mutagenic agents present a 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 DANN-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 mutagenic carcinogens maintaining cellular homeostasis and detoxifying enzymes and anti-oxygen defense mechanisms in the inactivation of genotoxic carcinogens. Part three focuses on DNA repair and the consequences and repair of oxidative DNA damage; the plasticity of DNA damage response during cell differentiation and tumor suppressor protein-mediated regulation of base excision repair in response to DNA damage. The concluding parts of the book discuss apoptosis and epigenetic mechanisms. The book will be essential reading for postgraduate students and scientific researchers working in environmental health, medicine and genetic toxicology.
Main Description
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.
Back Cover Copy
So far, there is general agreement that for genotoxic carcinogens no threshold can be identified. However, there are examples that the shape of the dose-responses of DNA adducts and mutations differ and it is also evident that the dose response for mutations will reach the background mutation frequency. This implies, that at low doses the mutation rate induced by a genotoxic/mutagenic carcinogen becomes indistinguishable from the background. Moreover, the array of cellular defence mechanisms such as metabolic inactivation, DNA-repair and apoptosis makes it unlikely that a single event overcomes these barriers to cancer. This confirms the experimental evidence of NOELs for carcinogenic and mutagenic effects in repeated dose studies in animals. In this book the different cellular defence mechanisms and their regulation are described. 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 the notion that even low exposures to genotoxic/mutagenic agents present a cancer risk is to be questioned.
Back Cover Copy
The Cellular Response to the Genotoxic Agent: The Question ofThreshold for Genotoxic Carcinogens describes the different cellulardefence 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.
Back Cover Copy
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.
Table of Contents
Introduction: The rationale for thresholds for genotoxic carcinogens
Threshold effects observed in experimental studies: Mechanisms responsible for the chromosome and gene mutations driving carcinogenesis: implications for dose-response characteristics of mutagenic carcinogens
Dose-effect relationships of DANN-reactive liver carcinogens
DNA alkylation and repair after EEMS exposure: Where do the thresholds for mutagenic/clastogenic effects arise?
Metabolic inactivation of genotoxic reactants: Enzymatic detoxification of endogenously produced mutagenic carcinogens maintaining cellular homeostasis
Phase 2 detoxifying enzymes and anti-oxygen defense mechanisms in the inactivation of genotoxic carcinogens
DNA repair: Consequences and Repair of oxidative DNA damage
The plasticity of DNA damage response during cell differentiation: pathways and consequences
Tumor suppressor protein-mediated regulation of base excision repair in response to DNA damage
Apoptosis: Survival and death strategies in cells exposed to genotoxin
Different modes of cell death induced by DNA damage
Transcriptional inhibition by DNA damage as a trigger of cell death
Epigenetic mechanisms: The interplay between epigenetics and Gap junctionional intercellular communication
Index
Table of Contents provided by Publisher. All Rights Reserved.

This information is provided by a service that aggregates data from review sources and other sources that are often consulted by libraries, and readers. The University does not edit this information and merely includes it as a convenience for users. It does not warrant that reviews are accurate. As with any review users should approach reviews critically and where deemed necessary should consult multiple review sources. Any concerns or questions about particular reviews should be directed to the reviewer and/or publisher.

  link to old catalogue

Report a problem