Chemical Mutagens Principles and Methods for Their Detection

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 . . . . . . . . . . . . . . . . . . . . . . . . . .

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.