Chemical Mutagens

of Volume 3.- 24 History of Research on Chemical Mutagenesis.- I. Introduction.- II. War Gases.- III. Other Alkylating Agents.- IV. Nitroso Compounds.- V. Urethane.- VI. Alkaloids.- VII. Inorganic Salts.- VIII. Formaldehyde, Organic Peroxides.- IX. Nitrous Acid.- X. Calf Thymus DNA and Other Macromolecules, Carcinogens.- XI Phenols.- XII. Basic Dyes.- XIII. Purines.- XIV. Base Analogues.- XV. Epilogue.- XVI. References.- 25 Observations on Meiotic Chromosomes of the Male Mouse as a Test of the Potential Mutagenicity of Chemicals in Mammals.- I. Introduction.- II. Methods for Detecting Chromosome Aberrations.- A. Spermatogenesis in the Mouse.- B. Description of Methods.- C. Techniques for Preparation of Meiotic Chromosomes.- III. Experimental Results with Ionizing Radiation.- A. Spermatocyte Test on Treated Males.- B. F1 Translocation Test.- IV. Experimental Results with Chemical Mutagens.- A. Review of Results.- B. Detailed Results.- C. Evaluation of Results and Prospects of the Experimental Approach.- V. Acknowledgments.- VI. References.- 26 Techniques for Monitoring and Assessing the Significance of Mutagenesis in Human Populations.- I. Introduction.- II. Kinds of Information about Human Populations Needed for Monitoring.- III. Limitations and Advantages of Using Existing Population Records.- IV. Information Content of the Available Records.- V. Methods of Record Linkage.- VI. Relevant Data Obtained by Record Linkage.- A. Amount of Hereditary Disease.- B. Distinguishing the Monomeric and Multifactorial Parts.- C. Tests for a Mutation-Maintained Component.- D. Tests for a Selection-Maintained Component.- VII. Future Accessibility of Diagnostic Data.- VIII. Mutagenesis and the Search for an Optimum Environment for Man.- IX. Conclusions for Geneticists.- X. References.- 27 Specific-Locus Mutational Assay Systems for Mouse Lymphoma Cells.- I. Introduction.- II. HGPRT Locus.- III. TK Locus: General Principles.- IV. TK Locus in a Mutational Assay System.- V. Concluding Remarks.- VI. Acknowledgments.- Appendix I: Cell Material and Techniques.- A. Cells.- B. Media (Nonselective Suspension—Growth and Cloning)..- C. Mutant Stocks.- D. Selective Media.- E. Thymidine Kinase Assay.- F. Spontaneous Mutation Rates.- G. Maintaining Cultures with Low Mutant Background.- H. Mutagen Assay (Forward).- I. Mutagen Assay (Reverse).- Appendix II: The Mycoplasma Menace.- VII. References.- 28 Approaches to Monitoring Human Populations for Mutation Rates and Genetic Disease.- I. Introduction.- II. Theoretical Importance of Measurements in Man.- III. Practical Importance of Human Genetic Monitoring.- IV. Study of Mutation at the Molecular Level.- V. Critique of Genetic Monitoring Based on Electrophoresis.- VI. Does the Initial Approach Meet the Criteria for a Satisfactory Monitoring System?.- VII. Estimates of the Magnitude of Effort Required.- VIII. Importance of Accurate Information.- IX. Some Technological Requirements.- X. Assessment of Technological Possibilities (Using Electrophoresis).- A. Sample Collection and Preparation.- B. Electrophoretic Separation.- C. Detection Using Immunological Methods.- XI. Methods Based on Activity Measurements.- A. Enzyme Variant Scanning.- B. Isozyme Scanning.- C. Enzyme Group Evaluation.- XII. Low Molecular Weight Substances.- A. Scanning for Screen Evaluation.- B. Automation of Screening Methods for Low Molecular Weight Substances.- XIII. Confirmatory Analyses, Genetic Follow-up, and Data Reduction.- XIV. Genetic Monitoring as a National Problem.- A. Cost/Benefit Considerations—Does the Potential Total Benefit Exceed the Total Cost?.- B. Benefits to Patients.- C. Benefits to Society.- D. Benefits to Research, Medical, and Decision-Making Communities.- E. Ethical Considerations.- XV. Conclusions.- XVI. References.- 29 Repair of Chemical Damage to Human DNA.- I. Introduction.- II. Sequence of Molecular Events in Experiments with Mutagenic and Carcinogenic Agents.- A. Typical Test Systems.- B. Introduction of the Agent.- C. Effect of Serum in the Treatment Medium.- D. Active and Nonactive Forms of Agents.- E. Local Dose to the Cellular DNA.- F. Induction and Repair of DNA Lesions.- G. Residual (Unrepaired) Lesions.- III. What Can DNA Repair Studies Tell Us?.- A. Extent of Repair.- B. Nature of the Repair Event.- C. Nature of the Lesion.- IV. Methods of Studying Repair.- A. Thymidine Uptake.- B. Unscheduled Synthesis.- C. Repair Replication.- D. Excision of UV-Induced Pyrimidine Dimers.- E. Photolysis of 5-Bromodeoxyuridine.- V. The Two Forms of Repair as Measured by BrUra Photolysis.- A. Ionizing-Type Repair.- B. UV-Type Repair.- VI. Classification of DNA-Damaging Chemical Agents According to the Repair Sequence Induced.- A. Ionizing-Type Repair after Chemical Damage.- B. UV-Type Repair after Chemical Damage.- VII. Xeroderma Pigmentosum and UV-Type Repair after Chemical Damage to DNA.- VIII. Summary of Present Interpretations.- IX. Acknowledgments.- X. References.- 30 Tradescantia Stamen Hairs: A Radiobiological Test System Applicable to Chemical Mutagenesis.- I. Introduction.- II. Techniques and Procedures.- A. Cultivation of Plants.- B. Screening the Plants.- C. Selection and Maintenance of Cuttings for Experimental Purposes.- D. The Flower.- E. Flower Production Records.- F. Numbers of Cuttings and Stamens Required.- G. Handling the Cuttings during Experimentation.- H. Types of Aberrations Found in Stamen Hairs.- I. Definition of a Mutant or Aberrant Event.- J. Loss of Reproductive Integrity (Stamen-Hair Stunting).- K. Preparation of Materials for Scoring.- L. Scoring Procedures.- III. Characteristic Data Obtained from the Stamen-Hair System.- IV. Summary.- V. Acknowledgments.- VI. References.- 31 Detection of Genetically Active Chemicals Using Various Yeast Systems.- I. Brief Description of the Yeasts Used in Genetic Research.- II. Techniques.- A. Media.- B. Culturing Yeast and Genetic Analysis.- C. Preparations of Synchronous Cultures.- D. Maintenance of Stock Cultures.- III. Treatment Conditions.- A. Treatment in Suspension.- B. Spot Test on Plates.- IV. Systems Used to Detect Mutagenicity of Chemicals.- A. Forward Mutation.- B. Reverse Mutation.- C. Mutagenesis in Meiotic Cells.- D. Cytoplasmic Inheritance.- V. Evaluation of Mutagenesis Experiments and Complications.- A. Mutation Fixation and Mutation Expression.- B. Dose-Response Curves.- VI. The Problem of Metabolic Activation.- VII. Mitotic Recombination.- A. Mitotic Crossing-Over.- B. Mitotic Gene Conversion.- VIII. Methods Used to Increase Sensitivity to Genetically Active Agents.- IX. General Evaluation.- X. Acknowledgments.- XI. References.- 32 Total Reproductive Capacity in Female Mice: Chemical Effects and Their Analysis.- I. Introduction.- II. Oocyte Development and Responses to Radiation Effects.- III. General Procedure.- IV. Fertility Effects of Alkylating Chemicals on Female Mice.- V. Delayed Pathological and Survival Effects in Chemically Treated Female Mice in the Total Reproductive Capacity Experiment.- VI. Importance of Using Females in Fertility Studies.- VII. Need for Assay Systems in Female Mice to Measure Induced Heritable Genetic Damage.- VIII. References.- 33 Insect Chemosterilants as Mutagens.- I. Introduction.- II. Screening of Chemosterilants.- III. Classification of Chemosterilants.- IV. Conclusion.- V. References.- 34 The Literature of Chemical Mutagenesis.- I. Introduction.- A. Restatement of an Old Problem.- B. Chemical Mutagenesis and Its Literature.- II. The State of Chemical Mutagenesis Literature.- III. Sources and Types of Chemical Mutagenesis Literature.- IV. Organization of Chemical Mutagenesis Information.- A. General Methods.- B. Specialized Methods.- V. Some Suggestions for Improving Literature Control.- VI. Conclusion.- VII: Acknowledgments.- Author Index.