Principles of Genetic Toxicology, Softcover reprint of the original 1st ed. 1980

The field of genetic toxicology is a relatively new one which grew out of the studies of chemical mutagenesis and modern toxicology. Considering that systematic practices to detect chemical mutagenesis are only a little over thirty years old, this field has evolved very rapidly with an abundance of methods for identifying chemical mutagens. To evalulate the usefulness of the methods and to select the assay which will yield the most important information under practical conditions requires the broad experience such as that which Dr. Brusick has acquired over the last decade. Since this field is expanding very rapidly and new test­ ing methods are being recognized, it should be kept in mind that revisions may have to be made during the next five to ten years. The need for such a book has been obvious to us, particularly since training courses and workshops on genetic toxicology are being organized which find it beneficial to utilize established guidelines and since the reports in the literature do not always describe in detail how the work was carried out during laboratory testing. In addition to his broad background in genetics, Dr. Brusick has had much practical experience, having organized and directed the most extensive laboratory for mutagen testing. I am most pleased to see this volume, for which there is an ever-increasing need. Alexander Hollaender Associated Universities, Inc. 1717 Massachusetts Avenue, N.W.

1 Origins of Genetic Toxicology.- The History of Genetic Toxicology.- Technology Transfer to Applied Genetics.- The Components of Genetic Toxicology.- References.- 2 Fundamentals of Genetic Toxicology.- Basic Genetics for Toxicologists.- Gene Structure.- Gene Function.- The Cell Cycle and Chromosome Mechanics in Somatic and Germ Cells.- DNA Alterations Resulting in Genotoxic Effects in Cells: Mechanisms and Categorization.- A Classification Scheme for Genotoxic Effects.- Repair of DNA Damage.- References.- 3 The Consequences of Genotoxic Effects in Humans and Other Mammals.- Gene Pool Consequences.- The Direct Effect of Mutagens on the Transmissible Gene Pool.- The Relationship of Genotoxic Effects to Other Toxicologic End Points.- Relationship of Potency between Mutagenicity Assays and in Vivo Oncogenicity.- References.- 4 Screening Chemicals for Genotoxic Properties.- and Background.- Characteristics of Adequate Screening Tests.- The Type(s) and Number(s) of End Points Detected.- The Metabolic Capability of the Test or Associated Activating System.- Reliability/Reproducibility.- Facilities.- Strategies for Test Battery Development.- General Philosophy.- Approaches to Test Battery Development.- Recommendations for Group I Tests.- Interpretation of Data from Screening Tests.- The Use of Controls in in Vitro and in Vivo Testing.- Approaches to Data Analysis and Interpretation.- References.- 5 Genetic Risk Estimation.- Definition of Risk.- Risk Estimation in Somatic and Germ Cells.- Somatic Cell Risk.- Germ Cell Risk.- Relationship of the Route of Exposure to Total Body Dose.- Relationship of the Route of Exposure to Metabolism.- Blood/Gonadal Barriers.- Molecular Dosimetry of Chemical Mutagens.- Measuring the Genotoxic Effect.- Approaches to Germ Cell Risk Using Animal Models.- Extrapolating Data from Short-Term Tests to Humans.- Extrapolation of in Vitro Data Directly to in Vivo Responses.- Threshold.- References.- 6 Applications of Genetic Toxicology to Environmental and Human Monitoring.- Monitoring Techniques.- Occupational Monitoring.- Environmental Monitoring.- References.- 7 The Genetic Toxicology Laboratory.- General Laboratory Areas.- Chemical Storage and Waste Disposal.- Laboratory Safety and Employee Monitoring.- Good Laboratory Practices Requirements.- References.- 8 Descriptions of Genetic Toxicology Assays.- General Classification of Genetic Toxicology Assays.- Description of Common Assays for Gene Mutation.- Microbial.- Mammalian Cells in Vitro.- Insects.- Mammals.- Tests for Chromosome Aberrations.- Microbial.- Mammalian Cells in Vitro.- Insect Tests for Chromosome Effects.- Mammals.- Tests for Primary DNA Damage.- Microbial Tests.- Cultured Mammalian Cell Repair Assays.- SCE Analysis.- Insects.- In Vivo Mammalian Primary DNA Damage.- In Vitro Cell Transformation.- References.- 9 Sample Study Designs.- Selected Study Designs.- Protocol I: Ames Salmonella/Microsome Plate Assay.- Materials.- Test Procedures.- Evaluation Criteria.- Surviving Populations.- Dose-Response Phenomena.- Control Tests.- Evaluation Criteria for Ames Assay.- Relation between Mutagenicity and Carcinogenicity.- References.- Protocol 2: Mitotic Recombination in S. cerevisiae Strain D3.- Dosing Procedure.- Method.- Evaluation Criteria.- References.- Protocol 3: Mitotic Gene Conversion in S. cerevisiae Strain D4.- Dosing Procedure.- Method.- General Evaluation Criteria.- Surviving Populations.- Dose-Response Phenomena.- Control Tests.- Evaluation Criteria for the Preincubation Plate Incorporation Assays Using Yeast Strain D4.- Reproducibility.- References.- Protocol 4: Mitotic Recombination in S. cerevisiae Strain D5.- Dosing Procedure.- Method.- Evaluation Criteria.- References.- Protocol 5: L5178Y TK+/?Mouse Lymphoma Forward Mutation Assay.- Materials.- Indicator Cells.- Media.- Control Articles.- Sample Forms.- Experimental Design.- Dose Selection.- Mutagenicity Testing.- Preparation of 9000g Supernatant (S9).- Assay Acceptance Criteria.- Assay Evaluation Criteria.- Reference.- Protocol 6: Chromosome Aberrations in Chinese Hamster Ovary Cells.- Materials.- Indicator Cells.- Medium.- Control Articles.- Experimental Design.- Toxicity and Dose Determination.- Cell Treatment.- Preparation of S9 Reaction Mixture.- Staining and Scoring of Slides.- Evaluation Criteria.- Reference.- Protocol 7: Sister Chromatid Exchange in Human Lymphocytes.- Materials.- Experimental Design.- Option 1.- Option 2.- Staining and Scoring of Slides.- Evaluation Criteria.- Reference.- Protocol 8: Sister Chromatid Exchange in Chinese Hamster Ovary Cells.- Materials.- Experimental Design.- Toxicity and Dose Determination.- Cell Treatment.- Preparation of S9 Reaction Mixture.- Staining and Scoring of Slides.- Evaluation Criteria.- References.- Protocol 9: Determination of Unscheduled DNA Synthesis in Human WI-38 Cells.- Materials.- Experimental Design.- Dose Selection.- Nonactivation Assay.- Activation Assay.- Extraction of DNA.- DNA Analysis.- Preparation of 9000g Supernatant (S9).- Evaluation Criteria.- Reference.- Protocol 10: Unscheduled DNA Synthesis in Rat Liver Primary Cell Cultures.- Materials.- Experimental Design.- Dose Selection.- UDS Assay Method.- Evaluation Criteria.- Reference.- Protocol 11: In Vitro Transformation of BALB/3T3 Cells.- Materials.- Experimental Design.- Dose Selection.- Transformation Assay.- Scoring of Transformed Foci.- Assay Acceptance Criteria.- Assay Evaluation Criteria.- References.- Protocol 12: Microbial Host-Mediated Assay.- Materials.- Experimental Design.- Animal Husbandry.- Dose Selection.- Route of Administration.- Test and Control Articles.- Bacteria Administration and Recovery.- Cell Plating for Survival and Mutant Determinations.- References.- Protocol 13: Bone Marrow Cytogenetic Analysis in Rats.- Materials.- Experimental Design.- Animal Husbandry.- Dose Selection.- Route of Administration.- Methodology.- Evaluation Criteria.- References.- Protocol 14: Dominant Lethal Assay in Rats.- Materials.- Experimental Design.- Animal Husbandry.- Dose Selection.- Route of Administration.- Methodology.- References.- Protocol 15: Heritable Translocation Assay in Mice.- Materials.- Experimental Design.- Animal Husbandry.- Dose Selection.- Methodology.- References.- Protocol 16: Mouse Micronucleus Assay.- Materials.- Experimental Design.- Animal Husbandry.- Dose Selection.- Dosing Schedule and Route of Administration.- Extraction of Bone Marrow.- Preparation of Slides.- Screening the Slides.- Evaluation Criteria.- References.- Protocol 17: Mouse Sperm head Abnormalities.- Materials.- Experimental Design.- Animal Husbandry.- Dose Selection.- Dosing Schedule and Route of Administration.- Preparation of Sperm Suspension.- Evaluation Criteria.- References.- Protocol 18: Somatic Mutation Assay in the Mouse (Spot Test).- Materials.- Animals.- Control Articles.- Experimental Design.- Animal Husbandry.- Dose Selection.- Route of Administration.- Treatment.- Spot Observation.- References.- Protocol 19: Test for Loss of X and Y Chromosomes in D. melanogaster.- Materials.- Experimental Design.- Solubility Testing.- Palatability and Toxicity Testing.- Fertility Testing.- Test Size.- Procedure.- Collection of Males.- Dosing.- Mating and Scoring.- Data Analysis.- Reference.- Protocol 20: Heritable Translocation Test in D. melanogaster.- Materials.- Experimental Design.- Solubility Testing.- Palatability and Toxicity Testing.- Fertility Testing.- Test Size.- Procedure.- Collection of Males.- Dosing.- Mating and Scoring.- Data Analysis.- Reference.- Protocol 21: Sex-Linked Recessive Lethal Test in D. melanogaster.- Materials.- Experimental Design.- Solubility Testing.- Palatability and Toxicity Testing.- Fertility Testing.- Test Size.- Procedure.- Collection of Males.- Dosing.- Mating and Scoring.- Data Analysis.- References.- Appendices.- Appendix A: Preparation of S9 Liver Homogenates.- Induction of Microsomal Enzymes.- Preparation of the S9 Fraction.- Preparation of the S9 Mix.- References.- References.- Appendix C: Selected References and Reviews of Genetics and Genetic Toxicology.