Volume 8 of Chemical Mutagens covers a wide range of topics in this continuously changing field. This volume includes chapters on the detection of genetic damage in mammalian sperm both at specific loci and over the entire genome. The discussion of in vitro techniques for working with mammalian cells covers not only specific locus assays but also cellular activation systems. Another chapter extensively discusses the need for a revised protocol for the micronucleus assay. Structure activity relationships are investigated in a chapter dealing with hair dye constituents. One of the most comprehensive chapters deals with problems associated with the detection of mutagenic effects in defined human populations. Finally, there is a detailed presentation of a comprehensive study tabulating the genetic bioassay data on some known or suspected human carcinogens. In keeping with our policy of publishing important legislation in the area of chemical mutagens, we have also included the Council of the European Communities Directive of 18 September 1979. Frederick J. de Serres Research Triangle Park, North Carolina vii Contents Chapter 1 Detection of Effects of Mutagens in Human Populations George R. Hoffmann 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2. Monitoring Progeny for Evidence of Germ-Cell Mutations. . . . . 3 2. 1. The Classical Approach: Phenotypic Monitoring . . . . . . . 3 2. 2. Monitoring for Changes in Gene Products . . . . . . . . . . . 7 3. Detection of Gene Mutations in Somatic Cells. . . . . . . . . . . . . 9 3. 1. Drug-Resistant Lymphocytes . . . . . . . . . . . . . . . . . . . . . . 9 3. 2. Hemoglobin Variants . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 4. Nongenetic Indicators of Mutagen Exposure . . . . . . . . . . . . . 21 4. 1. Alkylation of Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 4. 2. DNA Damage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
New developments in the study of environmental mutagens continue to evolve in this rapidly emerging field. In Volume 7 of Chemical Mutagens, we have focused on various new techniques for the detection of genetic damage in somatic cells and germ cells of mammals and the use of lower eukaryotic microorganisms to detect aneuploidy as well as other types of genetic damage. Attention has also been given to the role of in vitro metabolic activation as a mechanism for modifying the genetic effects of different environmental chemicals. In a chapter on compar ative mutagenesis, reaction kinetics and their relationship to the mu tagenic action of monofunctional alkylating agents in higher eukaryotic organisms are examined. In another chapter, the pharmacology and toxicology of nitrites and nitrates, which are in widespread distribution in the environment, are discussed in detail. The books in this series have provided a mechanism for the publication of many important new developments in the study of the genetic effects of environmental chemicals. This series was launched by Dr. Alexander Hollaender who, beginning in 1971, edited Volumes 1-4 and then coedited Volumes 5-7. The success of his lO-year effort with these volumes is another testimony to Dr. Hollaender's many contri butions to the field of environmental mutagenesis. As Dr.
As a result of the industrial revolution, man's technological achievements have been truly great, increasing the quality of life to almost unimagined proportions; but all this progress has not been accomplished without equally un imagined health risks. Sufficiently diagnostic short-term assay procedures have been developed in recent years for us to determine that there are mutagenic agents among thou sands of chemicals to which the human population is exposed today. These chemicals were not significantly present prior to the indus trial revolution. As of today, there are no procedures available which have been adequately demonstrated to assess individual sus ceptibility to genotoxic exposures, and as a result we have had to rely on extrapolating toxicological data from animal model systems. The question is can we afford to allow such an increased environ mental selection pressure via mutagenic exposures to occur without expecting adverse long-term effects on our health. It is apparent from this line of reasoning that what is lacking and immediately needed are test procedures that can be applied to humans to assess genotoxic exposure as well as individual susceptibility to it. There have already been two conferences which have focused at tention on this research area. "Guidelines for studies of human populations exposed to mutagenic and reproductive hazards" (A. D. Bloom, ed., March of Dimes Birth Defects Foundation, White Plains, New York, 1981) and "Indicators of genotoxic exposure in humans" (Banbury Report 13, B. A. Bridges, B. E. Butterworth, and I. B.
Volume 8 of Chemical Mutagens covers a wide range of topics in this continuously changing field. This volume includes chapters on the detection of genetic damage in mammalian sperm both at specific loci and over the entire genome. The discussion of in vitro techniques for working with mammalian cells covers not only specific locus assays but also cellular activation systems. Another chapter extensively discusses the need for a revised protocol for the micronucleus assay. Structure activity relationships are investigated in a chapter dealing with hair dye constituents. One of the most comprehensive chapters deals with problems associated with the detection of mutagenic effects in defined human populations. Finally, there is a detailed presentation of a comprehensive study tabulating the genetic bioassay data on some known or suspected human carcinogens. In keeping with our policy of publishing important legislation in the area of chemical mutagens, we have also included the Council of the European Communities Directive of 18 September 1979. Frederick J. de Serres Research Triangle Park, North Carolina vii Contents Chapter 1 Detection of Effects of Mutagens in Human Populations George R. Hoffmann 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2. Monitoring Progeny for Evidence of Germ-Cell Mutations. . . . . 3 2. 1. The Classical Approach: Phenotypic Monitoring . . . . . . . 3 2. 2. Monitoring for Changes in Gene Products . . . . . . . . . . . 7 3. Detection of Gene Mutations in Somatic Cells. . . . . . . . . . . . . 9 3. 1. Drug-Resistant Lymphocytes . . . . . . . . . . . . . . . . . . . . . . 9 3. 2. Hemoglobin Variants . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 4. Nongenetic Indicators of Mutagen Exposure . . . . . . . . . . . . . 21 4. 1. Alkylation of Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 4. 2. DNA Damage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
New developments in the study of environmental mutagens continue to evolve in this rapidly emerging field. In Volume 7 of Chemical Mutagens, we have focused on various new techniques for the detection of genetic damage in somatic cells and germ cells of mammals and the use of lower eukaryotic microorganisms to detect aneuploidy as well as other types of genetic damage. Attention has also been given to the role of in vitro metabolic activation as a mechanism for modifying the genetic effects of different environmental chemicals. In a chapter on compar ative mutagenesis, reaction kinetics and their relationship to the mu tagenic action of monofunctional alkylating agents in higher eukaryotic organisms are examined. In another chapter, the pharmacology and toxicology of nitrites and nitrates, which are in widespread distribution in the environment, are discussed in detail. The books in this series have provided a mechanism for the publication of many important new developments in the study of the genetic effects of environmental chemicals. This series was launched by Dr. Alexander Hollaender who, beginning in 1971, edited Volumes 1-4 and then coedited Volumes 5-7. The success of his lO-year effort with these volumes is another testimony to Dr. Hollaender's many contri butions to the field of environmental mutagenesis. As Dr.
Ecotoxicity and Human Health emphasizes the relationships between toxicity, ecological systems, and human health. It focuses on the extent and nature of hazardous waste sites and how their effects may be studied in humans and other systems, using in vitro models, biomarkers of cellular and molecular damage, and animal models. It also includes considerable information on bioremediation, legal and regulatory issues, public perceptions and societal responses, quantitative modeling and analysis, and international directives. One of the unique features of Ecotoxicity and Human Health is its coverage of the legislative actions that have occurred over the past two decades and which have most affected the issue of hazardous waste. The book discusses the Superfund Statute, the Resource Conservation and Recovery Act (RCRA), the Toxic Substances Control Act (TSCA), the Ocean Dumping Act of 1972, the Rio Conference, United Nations Declarations, EC Regulations and Directives, and selected state legislation.
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