The ready acceptance and wide demand for copies of the first two volumes of Chemical Mutagens: Principles and Methods Jar Their Detection have demon strated the need for wider dissemination of information on this timely and urgent subject. Therefore, it was imperative that a third volume be prepared to include more detailed discussions on techniques of some of the methods that were presented from a theoretical point of view in the first two volumes, and to update this rapidly expanding field with current findings and the new developments that have taken place in the past three years. Also included is a special chapter by Dr. Charlotte Auerbach giving the historical background of the discovery of chemical mutagenesis. Methods for recognizing mutagenic compounds in vitro are a necessary preliminary step toward arriving at satisfactory solutions for recognizing significant mutation rates in man, which must be done before our test tube methods of detection can be considered reliable. Two chapters in this volume make important contributions to this problem. Due to the increasing activity in efforts to perfect techniques for detecting chemical mutagens and their effects on man, it is planned to continue this series of volumes as necessary to keep abreast of current findings.
Inhalt
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 Capa…