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v. 6 ISBN 9780306403644
目次
1 Chemical Mutagens and Sister-Chromatid Exchange.- 1. Introduction.- 2. Sister-Chromatid Exchange as a Measure of Chromosome Damage.- 3. Systems and Methods t2.- 4. Summary.- 5. References.- 2 Modification of Mutagenic Activity.- 1. Introduction. 41 2. Factors That Influence Metabolic Activation t2.- 3The Detection of Chemical Mutagens/Carcinogens by DNA Repair and Mutagenesis in Liver Cultures.- 1. Introduction.- 2. Types of Chemical Carcinogens.- 3. Metabolic Activation Capability of Liver.- 4. Liver Cultures.- 5. Carcinogen Metabolism in Liver Cultures.- 6. Hepatocyte Primary Culture/DNA Repair Assay.- 7. Mutagenesis of Rat Liver Epithelial Lines.- 8. Hepatocyte-Mediated Mutagenesis of Rat Liver Epithelial Lines.- 9. Discussion.- 10. References.- 4 Commercial Screening of Environmental Chemicals.- 1. Introduction.- 2. Transfer of Technology.- 3. Goals of Genetic Toxicology in Chemical Safety Evaluation.- 5. Legal Operation Requirements.- 6. Summary.- 7. References.- 5 Determining the DNA-Modifying Activity of Chemicals Using DNA-Polymerase-Deficient Escherichia coli.- 1. Introduction.- 2. Materials and Methods.- 3. Standard Assay.- 4. Modified Assay.- 5. Microsomal Activation.- 6. Results and Discussion.- 7. Comparison of the Pol A and Salmonella Assays.- 8. References.- 6 Screening of Environmental Chemical Mutagens by the Rec-Assay System with Bacillus subtilis.- 1. Introduction.- 2. Principles and Related Background of the Rec-Assay.- 3. Experimental Procedures.- 5. Rec-Assays on Chemical Carcinogens.- 7 Transformation of Syrian Hamster Embryo Cells by Diverse Chemicals and Correlation with Their Reported Carcinogenic and Mutagenic Activities.- 1. Introduction.- 2. Mammalian Cell Transformation Systems as Prescreens for Identifying Carcinogens in the Environment.- 3. Hamster Embryo Cell in Vitro Carcinogenesis Bioassay.- 4. Correlation of Transformation Response with Reported Carcinogenicity and Mutagenicity.- 5. Metabolic Activation.- 6. A Battery vs. a Tier of Short-Term Tests for Identifying Potentially Carcinogenic Chemicals.- 7. Conclusions.- 8. References.- 8 Chemical Mutagenesis in the Silkworm.- 1. Introduction.- 2. Methods for Mutation Detection in the Silkworm.- 3. Procedures for Administration of Chemicals.- 5. Mosaics and Delayed Mutagenesis.- 6. Exploitation of a Sensitive Test System with Oocytes.- 7. Screening of Environmental Mutagenic Compounds.- 8. Modification of Mutagenicity by Metabolic Activation.- 9. Conclusion.- 10. References.- 9 The Use of Short-Term Tests in the Isolation and Identification of Chemical Mutagens in Complex Mixtures.- 1. Introduction.- 2. Extraction Methodology.- 3. Mutagenesis Assay Methodology.- 10 Mathematical Analysis of Mutation-Induction Kinetics.- 1. Introduction.- 2. Definitions.- 3. Stochastic Description of Mutagenesis and Killing.- 4. Formal Dose-Response Patterns.- 5. The Linear Response Pattern (Lk,Lm).- 6. Nonlinear Response Patterns.- 7. Illustrative Calculations of Yield Curves.- 8. Relative Mutagenic Efficiency (RME).- 9. Stochastic Dependence of Mutation and Killing.- 10. Repair-Mediated Mutagenesis.- 11. Concluding Remarks.- 12. Summary.- 13. Appendix t2.- 11 Comparison of the Mutagenic Effect of Ultraviolet Radiation and Chemicals in Normal and DNA-RepairDeficient Human Cells in Culture.- 1. Introduction.- 2. Procedures.- 3. Evidence that Excision Repair Can Eliminate Potentially Cytotoxic and Mutagenic Lesions from DNA.- 12 Gene-Locus Mutation Assays in Diploid Human Lymphoblast Lines.- 1. Introduction.- 2. Exposure.- 4. Selection Systems.- 5. Experimental Observations.- 6. Discussion.- 7. References.- 13 The Need for Both in Vitro and in Vivo Systems in Mutagenicity Screening.- 1. Introduction.- 3. Correlations between Carcinogenicity and Mutagenicity in Salmonella.- 4. Construction of a Table of 465 Compounds with Known or Suspected Carcinogenic Activity (Table 4).- 5. Discussion of False Negatives from Table 4.- 6. Validation of Salmonella Testing as a Predictor of Carcinogenicity.- 7. Concluding Comments on Mutagenicity Testing.- 8. References.
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v. 7 ISBN 9780306407710
内容説明
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.
目次
1 Effects of Chemicals on Chromosome-Aberration Production in Male and Female Germ Cells.- 1. Introduction.- 2. Methods of Detecting Chromosome Aberrations Induced in Germ Cells.- 3. Male Germ Cells.- 3.1. Preparation Techniques.- 3.2. Chromosome Studies of Spermatogonial Mitoses.- 3.3. Chromosome Analysis in Spermatocytes after Treatment of Stem-Cell Spermatogonia.- 3.4. Chromosome Analysis in Spermatocytes after Treatment of Meiotic Prophase Stages.- 3.5. Analysis of Cleavage Stages after Treatment of Meiotic and Postmeiotic Male Germ Cells.- 4. Female Germ Cells.- 4.1. Preparation Techniques.- 4.2. Analysis of Chromosome-Aberration Induction in Oocytes.- 5. Interpretations and Conclusions.- 6. References.- 2 The Use of Immunological Techniques to Detect Cells of Rare Genotype.- 1. Introduction.- 2. Isolation of Antibodies Suitable for Detecting Mutants: Antibodies to Single and Multiple Amino Acid Differences in Proteins.- 2.1. General.- 2.2. Isolation Procedures and Examples.- 2.3. Detection of Monospecific Antibody in the Serum.- 3. Detection of Mutants with the Help of Antibodies.- 3.1. Hemoglobin System.- 3.2. Lactate Dehydrogenase-X System.- 3.3. Immunoglobulin-Allotype System.- 3.4. H-2 System.- 4. Conclusion.- 5. References.- 3 Metabolic Activation Systems in Vitro for Carcinogen/Mutagen Screening Tests.- 1. Introduction.- 2. Common Pathways for the Activation and Detoxification of Carcinogens/Mutagens.- 2.1. Enzymatic Activation Reactions That Introduce or Modify Functional Groups (Phase I Reactions).- 2.2. Enzymatic Conjugation (Phase II Reactions).- 2.3. Detoxification Reactions of Carcinogens/Mutagens.- 3. Subcellular Metabolic Activation Systems: Some General Remarks.- 3.1. Hepatic Postmitochondrial Supernatant (S-9) Fraction from Rats.- 3.2. Purified Subcellular Hepatic-Tissue Fractions (Enzymes) from Rat Liver and Other Sources.- 3.3. Species Variations in Hepatic Metabolic Activation Reactions.- 3.4. Metabolic Activation by Rodent Extrahepatic-Tissue Fractions.- 3.5. Carcinogen/Mutagen Activation by Human Liver (or Other Tissue) Enzymes.- 4. Cellular Metabolic Activation Systems.- 4.1. Cultured Cells That Possess Metabolic Activity.- 4.2. Assays That Use Cultured Mammalian Cells for Metabolic Activation.- 4.3. Evaluation of the Efficiency of Carcinogen/Mutagen Screening Tests That Use Intact Mammalian Cells for Metabolic Activation.- 5. Combination of in Vivo-in Vitro Screening Tests of Carcinogens/Mutagens: Recent Developments.- 6. Problems in the Extrapolation of Data Obtained in Vitro to the Intact Mammalian Organism.- 7. Conclusions.- 8. References.- 4 Microbial Metabolism of Environmental Chemicals to Mutagens and Carcinogens.- 1. Introduction.- 2. Definition of a Compound as a Promutagen.- 3. Chemicals That Can Be Activated to Environmental Mutagens and Carcinogens by Microorganisms.- 3.1. Azo Dyes.- 3.2. Glycosidase Conjugates.- 3.3. Nitroaryl and Heterocyclic Compounds.- 3.4. N-Hydroxy Aromatic Amides and Amines.- 3.5. Chemicals That Require Activation by Cytochrome-P-450-Dependent Monooxygenases.- 3.6. Ethidium Bromide.- 4. Role of the Intestinal Microflora in the Formation of Mutagens and Carcinogens.- 5. Short-Term Test Systems and the Role of Microorganisms in the Metabolism of Chemicals into Mutagens: Conclusions.- 5.1. Metabolic Systems of Indicator Organisms.- 5.2. Activation by Intestinal Microbial Flora and Short-Term Test Systems.- 6. Summary.- 7. References.- 5 Short-Term Tests for Chemicals That Promote Aneuploidy.- 1. Introduction.- 2. Test Systems.- 2.1. Meiotic Systems.- 2.2. Mitotic Systems.- 3. Discussion.- 3.1. Biological Relevance.- 3.2. Application.- 4. References.- 6 Nitrates and Nitrites: Ingestion, Pharmacodynamics, and Toxicology.- 1. Introduction.- 2. Major Sources of Human Exposure.- 2.1. Ingestion.- 2.2. Endogenous Synthesis.- 3. Flow in Humans.- 3.1. Ingestion and Endogenous Synthesis.- 3.2. Active Nitrate Transport from the Gastrointestinal Lumen.- 3.3. Plasma Levels of Pertinent Anions.- 3.4. Tissue Compartments and Nitrate Storage.- 3.5. Salivary Recirculation of Nitrate.- 3.6. Gastric Recirculation of Nitrate.- 3.7. Mammary Transport of Nitrate.- 3.8. Placental Transport of Nitrate.- 3.9. Nitrate and Nitrite Loss in Vivo.- 3.10. Nitrate in Human Urine.- 4. Suspected Health Consequences.- 4.1. Nitrate Ingestion: Tolerance to Acute Effects.- 4.2. Nitrate Ingestion: Possible Long-Term Effects.- 4.3. Ingestion and in Vivo Production of Nitrite.- 5. Reduction of Exposure.- 5.1. Cured Meats.- 5.2. Vegetables.- 5.3. Water.- 6. Summary.- 7. References.- 7 The Relation between Reaction Kinetics and Mutagenic Action of Monofunctional Alkylating Agents in Higher Eukaryotic Systems: Interspecies Comparisons.- 1. Introduction.- 2. Mechanism of Action of Alkylating Agents.- 3. Reaction of Alkylating Agents with DNA and Proteins.- 3.1. Alkylalkanesulfonates.- 3.2. Dialkylsulfates.- 3.3. Dialkylnitrosamines, Alkylnitrosamides, and Alkylnitrosoguanidines.- 3.4. Comparison of Reactivity.- 3.5. Significance of Alkyl Groups in DNA.- 4. Response to Alkylating Agents.- 4.1. Higher Plants.- 4.2. Drosophila.- 4.3. Mammals.- 5. Interspecies Comparisons.- 5.1. Effectiveness.- 5.2. Efficiency.- 5.3. Carcinogenicity.- 5.4. Problems for Future Work.- 6. Conclusions.- 7. References.- 8 The Human Leukocyte Test System.- 1. Introduction.- 2. Some Early Events during Human Leukocyte Stimulation...- 3. DNA Synthesis, Mitosis, and the Diversity of the Culture System.- 4. Differences in Mutagen Sensitivity of Leukocyte Subpopulations?.- 5. Fate of Chromosomal Damage during Successive Cell Cycles.- 6. Selected Examples of in Vivo Investigations with Human Leukocytes.- 6.1. Alcohol and Tobacco Smoke.- 6.2. Psychotropic Drugs.- 6.3. Illicit Drugs.- 6.4. Antiepileptic Drugs.- 7. Appendix: Standard Protocol for Human Leukocyte Culture Preparation.- 7.1. Contents of a Standard Leukocyte Culture.- 7.2. Preparation of Cultures.- 7.3. Preparation of Slides.- 7.4. 5-Bromodeoxyuridine-Labeling.- 7.5. A Note on Centromeric Sister-Chromatid Exchanges.- 8. References.- 9 The Activation of Chemicals into Mutagens by Green Plants.- 1. Introduction.- 2. Plant Activation of Promutagens.- 2.1. In Vivo Plant Activation.- 2.2. In Vitro Plant Activation.- 3. Deactivation of Mutagens by Plants.- 4. Response of Plant Genetic Assays to Known Mammalian Promutagens.- 4.1. Nitrosamines.- 4.2. s-Triazines.- 4.3. Maleic Hydrazide.- 4.4. Other Promutagens.- 5. Conclusion.- 6. References.- 10 Unscheduled DNA Synthesis in Mammalian Germ Cells-Its Potential Use in Mutagenicity Testing Gary A. Sega.- 1. Introduction.- 2. What Does the Occurrence of Unscheduled DNA Synthesis in Mouse Germ Cells Mean?.- 3. Procedures for Treating Animals with [3H]Thymidine and Chemical Mutagens.- 3.1. Injection of Mice with [3H]Thymidine.- 3.2. Treatment of Mice with Chemical Mutagens.- 4. Detection of Unscheduled DNA Synthesis in the Germ Cells.- 4.1. Procedures for Liquid Scintillation Counting.- 4.2. Autoradiographic Procedures.- 5. Germ-Cell Stages That Undergo Unscheduled DNA Synthesis When Exposed to Mutagenic Agents.- 6. Comparison of the Sensitivity of the Test for Unscheduled DNA Synthesis with That of Other Genetic Tests.- 7. Relationship between Genetic Effects and Unscheduled DNA Synthesis Induced by Mutagens.- 8. Development and Characterization of Mouse Stocks with Reduced Levels of Unscheduled DNA Synthesis in Their Germ Cells.- 9. Relevancy of the Test for Mammalian Germ-Cell Unscheduled DNA Synthesis Compared with That of Other Mutagenicity Tests.- 10. References.- 11 Aspergillus nidulans-An Organism for Detecting a Range of Genetic Damage.- 1. Introduction.- 2. Basic Biology.- 2.1. Life Cycle.- 2.2. Nuclear Cycle.- 3. General Methodology.- 3.1. Media.- 3.2. Growth and Collection of Conidial Sample.- 3.3. Removal of Germination-Inhibitory Substances.- 3.4. Method of Treatment.- 3.5. Other Techniques Associated with the Various Assays.- 3.6. Metabolic Activation.- 4. Assay Systems.- 4.1. Haploid Mutational Systems.- 4.2. Diploid Genetic Systems.- 4.3. Masked Genetic Damage: Examination of the "Normal Colonies".- 5. Concluding Remarks.- 6. References.
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v. 8 ISBN 9780306413360
内容説明
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 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
目次
1 Detection of Effects of Mutagens in Human Populations.- 1. Introduction.- 2. Monitoring Progeny for Evidence of Germ-Cell Mutations.- 3. Detection of Gene Mutations in Somatic Cells.- 4. Nongenetic Indicators of Mutagen Exposure.- 5. Testing for Mutagenic Substances in Body Fluids.- 6. Detection of Altered Sperm.- 7. Summary.- 8. References.- 2 The Use of Intact Cellular Activation Systems in Genetic Toxicology Assays.- 1. Introduction.- 2. Mammalian Cell Mutagenesis.- 3. Bacterial Mutagenesis.- 4. Sister Chromatid Exchange and Chromosome Aberrations.- 5. Cell-Mediated Transformation.- 6. Cytotoxicity and Nucleic Acid Interactions.- 7. Discussion.- 8. Summary.- 9. References.- 3 The Mouse Spot Test As a Predictor of Heritable Genetic Damage and Other Endpoints.- 1. Introduction.- 2. Relation to Measures of Heritable Mutations.- 3. Relation to Other Endpoints.- 4. Summary.- 5. References.- 4 The Bone Marrow Micronucleus Assay: Rationale for a Revised Protocol.- 1. Introduction.- 2. Kinetics of Erythropoiesis.- 3. Rationale for the Basic Aspects of the Protocol.- 4. Protocol.- 5. Statistical Analysis.- 6. Conclusions.- 7. References.- 5 Relationships between the Chemical Structure and Mutagenic Activity of Monocyclic Aromatic Amines.- 1. Introduction.- 2. Bacterial Strains.- 3. Experimental Methods.- 4. Chemicals.- 5. Mutagenicity Data and Their Interpretation.- 6. Possible Pitfalls in Studies of Structure-Activity Relationships.- 7. Conclusions.- 8. References.- 6 The Measurement of Recessive Lethal Mutations in the Mouse.- 1. Introduction.- 2. Haldane’s Method of Detecting Lethals.- 3. The Backcross Method of Detecting Lethals.- 4. Irradiation Treatment of Male Germ Cells.- 5. Irradiation Treatment of Female Germ Cells.- 6. Chemical Mutagen Induction of RecessiveLethal Mutations.- 7. Dominant Effects of Recessive Lethal Mutations.- 8. Conclusions.- 9. References.- 7 Chemically Induced Changes in Sperm in Animals and Humans.- 1. Introduction.- 2. The F0 Mouse Sperm Head Morphology Assay.- 3. The F1 Sperm Head Morphology Assay.- 4. Induced Sperm Abnormalities in Humans.- 5. Implications of Alterations in Human Sperm Quality.- 6. The Advantages of Sperm Assays.- 7. Recommendations for Future Research and Development.- 8. References.- 8 Mutational Analysis in Cultured Human-Hamster Hybrid Cells.- 1. Introduction.- 2. Origin of Specific Lethal Antisera and Human-Hamster Hybrid Cells.- 3. Characterization of the AL Hybrid.- 4. Mutation Studies.- 5. Conclusions.- 6. References.- 9 Genetic Toxicology of Some Known or Suspected Human Carcinogens.- 1. Introduction.- 2. Chemical Selection.- 3. Method of Literature Review.- 4. Results.- 5. Discussion.- 6. Summary and Conclusions.- 7. Appendix: Complete Data Base.- 8. References.- 10 Control of Commercial Chemicals: The Sixth Amendment to the Directive on Dangerous Chemical Substances (79/83 I/EEC) Adopted by the Council of the European Communities.- 1. Introduction.- 2. Text of the Sixth Amendment to the Directive on Dangerous Chemical Substances Adopted by the Council of the European Communities.- 3. References.
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v. 10 ISBN 9780306421716
内容説明
Volume 9 of Chemical Mutagens consists mainly of chapters discussing the development and validation of short-term assays to detect the mutagenic effects of environmental chemicals. These chapters include an assay with the grasshopper neuroblast, a comparison of mutagenic responses of human lung-derived and skin-derived diploid fibroblasts, a forward-mutation assay in Salmonella, a multigene sporulation test in Bacillus subtilis, a specific locus assay in mouse lymphoma cells, a study of the induction of bacteriophage lambda, and the granuloma pouch assay. In addition, there are two chapters on the identification of mutagens in cooked food and in human feces. Frederick 1. de Serres Research Triangle Park, North Carolina vii Contents Chapter 1 The Grasshopper Neuroblast Short-Term Assay for Evaluating the Effects of Environmental Chemicals on Chromosomes and Cell Kinetics 1 Mary Esther Gaulden, Jan C. Liang, and Martha J. Ferguson 1. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2. Embryo Supply. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 2. 1. Species. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 2. 2. Origin of Colonies . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 2. 3. Life Cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 2. 4. Colony Maintenance . . . . . . . . . . . . . . . . . . . . . . . . . 6 2. 5. Pathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 2. 6. Allergy to Grasshoppers . . . . . . . . . . . . . . . . . . . . . . 14 3. Grasshopper Egg, Embryo, and Cells . . . . . . . . . . . . . . . . . 14 3. 1. The Egg Shell and Membranes . . . . . . . . . . . . . . . . . 14 3. 2. Embryonic Development . . . . . . . .. . . . . . . . . . . . . . 17 3. 3. Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 4. Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 4. 1. Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 4. 2. Preparation of Embryos for Cell Analysis . . . . . . . . . 34 4. 3. Analysis of Mutagen Effects. . . . . . . . . . . . . . . . . 40 . . . 5. Response of the Grasshopper Neuroblast to Mutagens . . . . 50 5. 1. Reproducibility of Data . . . . . . . . . . . . . . . . . . . . . . . 50 5. 2. Radiation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 5. 3. Chemical Mutagens . . . . . . . . . . . . . . . . . . . . . . . . . .
目次
1 In Vivo Mutagenicity Testing Using Somatic Cells of Drosophila melanogaster.- 1. Introduction.- 2. Basic Developmental Biology of Drosophila.- 3. The Wing Mosaic System.- 4. The White/White-Coral Eye Mosaic System.- 5. The Unstable White-Zeste Eye Mosaic System.- 6. Exposure Techniques.- 7. Discussion.- 8. Conclusions.- 9. References.- 2 Structural and Metabolic Parameters Governing the Mutagenicity of Polycyclic Aromatic Hydrocarbons.- 1. Introduction.- 2. Activation Pathways of PAHs.- 3. Contribution of Different Activation Pathways to the Mutagenicity of PAHs.- 4. Metabolic Control of Mutagenic Intermediates of PAHs.- 5. Summary and Conclusions.- 6. Addendum: Recent Developments.- 7. References.- 3 Chromosomal Mutations: The Genetic Approach.- 1. Introduction.- 2. The Main Categories of Chromosomal Mutation.- 3. Genetic Detection of Aneuploidy in the Mouse.- 4. Reciprocal Translocations: Detection and Analysis.- 5. Detection and Study of Other Translocations and of Inversions.- 6. Detection and Study of Deletions.- 7. Conclusions.- 8. References.- 4 Cytogenetic Assays for Mitotic Poisons Using Somatic Animal Cells.- 1. Introduction.- 2. Mitotic Poisons and Their Genomic Effects.- 3. Assays with Diploid Mammalian Cells in Vitro.- 4. Assays with Bone Marrow Cells in Vivo.- 5. Assays with Grasshopper Embryos.- 6. Conclusions.- 7. References.- 5 Detection of Aneuploidy in Drosophila.- 1. Introduction.- 2. Issues.- 3. Assay Systems.- 4. Known Positives.- 5. Summary.- 6. References.- 6 Mammalian Cytogenetic and Genetic Tests for Nondisjunction.- 1. Introduction.- 2. Cytogenetic Tests.- 3. Genetic Test Systems with the Mouse.- 4. Summary and Conclusions.- 5. References.- 7 Using Repair-Deficient Chinese Hamster Ovary Cells to Study Mutagenesis.- 1. Introduction.- 2. Genetic and Biochemical Properties of Repair-Deficient Mutants.- 3. Hypersensitivity of Repair Mutants to DNA-Damaging Agents.- 4. Rapid Detection of DNA-Damaging Agents by Differential Cytotoxicity (DC).- 5. Conclusions.- 6. References.- 8 Transplacental Genotoxic Agents: Cytogenetic Methods for Their Detection.- 1. Introduction.- 2. Animal Studies.- 3. Human Studies.- 4. References.- 9 Computer Automation of Metaphase Finding, Sister Chromatid Exchange, and Chromosome Damage Analysis.- 1. Introduction.- 2. Historical Trends in Computer Automation.- 3. Development of a System for Cytogenetic Mutagenicity Testing.- 4. Future Prospects for Full Automation.- 5. References.- 10 Mutagen-Sensitive Mutants and Chemical Mutagenesis in Drosaphila.- 1. Introduction.- 2. Isolation and Localization of Mutants.- 3. Biochemical Characteristics.- 4. Larval Exposure.- 5. Adult Exposure.- 6. Maternal Effects.- 7. Storage Effect.- 8. Conclusions.- 9. References.- 11 Chromosomal Causes for Fertility Reduction in Mammals.- 1. Introduction.- 2. Numerical Chromosome Mutations of the Sex Chromosomes and Related Conditions.- 3. Structural Chromosome Anomalies.- 4. Combinations of Chromosome Mutants within One Carrier.- 5. Viable Unbalanced Progeny Obtained from Translocation Heterozygote Females and Males.- 6. Why is Chromosomal Infertility More Clearly Expressed in the Male Than in the Female? Consideration of X-Autosome Translocations.- 7. References.- 12 Mutagenesis and Plasmids.- 1. Introduction.- 2. Historical Overview of Plasmids.- 3. Survey of Thirty-Three R Plasmids.- 4. Mechanisms of Plasmid-Mediated Effects on Mutagenesis and Survival.- 5. References.- 13 Mutation in Somatic Cells as Determined by Electrophoretic Analysis of Mutagen-Exposed Chinese Hamster Ovary Cells.- 1. Introduction.-3. Results and Discussion.- 4. Summary.- 5. References.
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