In the rapidly developing field of environmental mutagenesis, the use of stand ardized protocols has permitted the evaluation of large numbers of chemicals for mutagenic and potential carcinogenic activity. In this sixth volume of Chemical Mutagens, the chapters by Perry, Williams, Rosenkranz and Leifer, Kada et al., Pienta, Tazima, Epler, and Rinkus and Legator provide a systematic listing of the chemicals that have been tested, bringing together both unpublished and previously published data. These chapters will serve as an important milestone by providing a convenient reference to tabulated test data with particular assay systems. Another important area of research is the modification of mutagenic activity. In the chapter by Sugimura and Nagao, factors that alter in vitro metabolic activation are discussed, whereas in the chapter by Maher and McCormick, the role of genetic heterogeneity is considered. Equally important is our need to obtain a better understanding of mutation-induction kinetics, and the mathematical analysis by Haynes and Eckardt provides an important step in this direction. An important new approach for the induction of specific locus mutations in human cells in culture is discussed in the chapter by Thilly and co-workers. We have also been concerned about the problems in the practical applica tion of various short-term tests in commerical testing laboratories. The prob lems emerging in the evaluation of potentially important new chemicals have been discussed in a chapter by Brusick et al.

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1 Chemical Mutagens and Sister-Chromatid Exchange.- 1. Introduction.- 1.1. Advantages of Studying Sister-Chromatid Exchange.- 1.2. Development of Modern Techniques.- 2. Sister-Chromatid Exchange as a Measure of Chromosome Damage.- 2.1. Variation in the Baseline Frequency of Sister-Chromatid Exchange.- 2.2. Induction of Sister-Chromatid Exchanges by Ultraviolet Light, X Rays, and Viruses.- 2.3. What Are Sister-Chromatid Exchanges?.- 2.4. Factors That Affect the Frequency of Sister-Chromatid Exchanges Induced by Chemicals.- 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.- 4.1. Hepatocyte Primary Cultures.- 4.2. Long-Term Epithelial Cultures.- 5. Carcinogen Metabolism in Liver Cultures.- 6. Hepatocyte Primary Culture/DNA Repair Assay.- 6.1. Autoradiographic Assay.- 6.2. Liquid Scintillation Counting 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.- 3.1. Approaches for Assay System Deployment in the Identification of Genotoxic Substances.- 3.2. Application of Test Results to Health and Safety Considerations.- 3.3. Application of Test Results to Management Decisions Concerning Chemical Development.- 4. Technical Operation Requirements.- 4.1. Facilities.- 4.2. Data Management and Control.- 4.3. Chemical Storage and Waste Disposal.- 5. Legal Operation Requirements.- 5.1. Laboratory Safety and Employee Monitoring.- 5.2. Good Laboratory Practices and Guidelines.- 6. Summary.- 7. References.- 5 Determining the DNA-Modifying Activity of Chemicals Using DNA-Polymerase-Deficient Escherichia coli.- 1. Introduction.- 2. Materials and Methods.- 2.1. Media.- 2.2. Preservation of Tester Strains.- 3. Standard Assay.- 3.1. Preparation of Cultures for Testing.- 3.2. Important Precautions.- 3.3. Procedure for the Pol A Assay.- 3.4. Preparation of Test Agents.- 3.5. Standards.- 4. Modified Assay.- 4.1. Modification of the Pol A1-Assay (Liquid Suspension).- 4.2. Procedure.- 5. Microsomal Activation.- 5.1. Preparation of Rat Liver S-9 Fraction.- 5.2. Plate Assay.- 5.3. Liquid Assay Procedure.- 6. Results and Discussion.- 6.1. Standard Assay.- 6.2. Modified (Liquid) Assay.- 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.- 3.1. Rapid Streak Method (without Metabolic Activation).- 3.2. Quantitative Analysis by the Spore Rec-Assay (with and without Metabolic Activation).- 3.3. Quantitative Liquid Method (with and without Metabolic Activation).- 4. Examples of Detection of Chemical Mutagens by the Rec-Assay Procedures.- 4.1. Food Additives.- 4.2. Pesticides.- 4.3. Metals.- 4.4. Miscellaneous.- 5. Rec-Assays on Chemical Carcinogens.- 6. References.- 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.- 3.1. Standardization of the Bioassay Procedure by the Use of Cryopreserved Cells.- 3.2. Criteria for Positive Response.- 4. Correlation of Transformation Response with Reported Carcinogenicity and Mutagenicity.- 4.1. Direct-Acting Alkylating Agents.- 4.2. Polycyclic Aromatic Hydrocarbons.- 4.3. Nitrosamines and Nitrosamides.- 4.4. Aromatic Amines, Aminoazo Dyes, and Nitro Compounds.- 4.5. Carcinogenic Metallic Salts.- 4.6. Miscellaneous Compounds.- 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.- 2.1. Correlation between Developmental Stages of the Silkworm and the Stages of Spermatogenesis and Oogenesis.- 2.2. Specific Locus Method.- 2.3. Dominant Lethal Method.- 2.4. Detection of Nondisj unction and Polyploidy.- 3. Procedures for Administration of Chemicals.- 3.1. Oral Administration.- 3.2. Injection.- 3.3. Soaking of Eggs in Chemical Solution.- 3.4. Gas (Aerosol) Treatment.- 4. Sensitivity.- 4.1. Strain Difference.- 4.2. Variation with the Progress of Germ-Cell Development.- 5. Mosaics and Delayed Mutagenesis.- 5.1. Preponderance of Mosaics.- 5.2. Delayed Mutagenic Effect.- 6. Exploitation of a Sensitive Test System with Oocytes.- 6.1. Effective Stage of Injected Chemicals in the Oocyte System.- 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.- 2.1. Rapid, Simple Extraction Methods.- 2.2. Class Fractionation.- 3. Mutagenesis Assay Methodology.- 3.1. Microbial Mutagenesis Assays.- 3.2. Comparative Mutagenesis.- 3.3. Precautions for the Use of Short-Term Mutagenicity Assays.- 4. References.- 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.- 6.1. Initial Slope of Yield Curves.- 6.2. Positions of Yield Maxima.- 6.3. Magnitude of Yield Maxima.- 6.4. Lethal Hit Units for Nonlinear Cases.- 6.5. Integral Yields for Nonlinear Cases.- 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 …