Chemical Mutagens

of Volume 1.- 1 Molecular Mechanisms of Mutations.- I. Introduction.- II. Causes and Types of Alterations of the Hereditary Material and Protection Against Them.- A. General Causes of Genetic Alterations.- B. Protective Mechanisms.- C. Types of Genetic Alterations.- D. Consequences of Genetic Alterations in Higher Organisms.- III. Detection of Chromosome Aberrations and Systems of Genetic Analysis.- A. Cytological Examination of Large Chromosome Aberrations.- B. Genetic Examination of Mutations.- C. Test Systems for Mammalian Investigations.- IV. Primary DNA Alterations and Their Genotypic and Phenotypic Consequences.- A. Nonhereditary DNA Alterations.- B. Mutagenic DNA Alterations.- C. Inactivating DNA Alterations.- D. Most Agents Induce Several Primary DNA Alterations.- E. Correlation of Agents Inducing Inactivating DNA Alterations with Other Effects.- V. The Effect of Different Agents on DNA and Chromosomes.- A. Incorporation of Base Analogs into DNA.- B. Effect of Nitrous Acid on Resting DNA.- C. Alkylating Agents.- D. N-Nitroso Compounds.- E. Hydroxylamines.- F. Agents Acting after Conversion to Hydroxylamines or Hydroxamates.- G. Other Free-Radical-Producing Agents.- H. Ultraviolet Light.- I. Inhibitors of DNA Synthesis.- J. Intercalating Agents.- K. Metals.- L. Mutator Genes.- VI. References.- 2 Correlation Between Teratogenic and Mutagenic Effects of Chemicals in Mammals.- I. Introduction.- II. Frequency of Effects of Chemicals.- III. Specificity of Action of Chemicals.- IV. Dose.- V. Species, Sex, and Strain Differences.- VI. Timing.- VII. Are Induced Malformations Due to Mutations?.- VIII. Mutagenicity and Teratogenicity Testing.- IX. Conclusion.- X. References.- 3 The Mutagenicity of Chemical Carcinogens: Correlations, Problems, and Interpretations.- I. Introduction.- II. Ultimate Carcinogenic Forms of Chemical Carcinogens Their Reactivities.- A. Alkylating Agents.- B. Potential Alkylating Agents.- C. Aromatic Amines and Amides.- D. 4-Nitroquinoline-1-oxide.- E. N-Hydroxypurines.- F. Polycyclic Aromatic Hydrocarbons.- G. Urethan.- H. N-Nitroso-N-phenylurea.- I. Metal Ions.- J. Conclusion.- III. Mutagenic Activity of Carcinogenic Chemicals.- A. Assay Systems.- B. Problems in Interpretation.- C. Alkylating Agents.- D. Potential Alkylating Agents.- E. Aromatic Amines and Amides.- F. Polycyclic Aromatic Hydrocarbons.- G. Urethan (Ethyl Carbamate).- H. Aflatoxins.- I. Mitomycin C.- J. Hydrazine.- K. Metals.- IV. Conclusions.- V. References.- 4 Effects on DNA: Chemical Methods.- I. Introduction.- II. Isolation of DNA.- III. Degradation of DNA.- A. Enzymatic Methods.- B. Chemical Methods.- IV. Methods of Separation of Products.- A. Chromatography.- B. Electrophoresis.- V. Methods of Detection and Identification of Products.- A. Spectroscopy.- B. Use of Radioactive Materials.- C. Mass Spectroscopy.- VI. References.- 5 Physical-Chemical Methods of the Detection of the Effect of Mutagens on DNA.- I. Introduction.- II. DNA Substrates for Physical Studies.- III. Physical Methods.- IV. Changes Resulting from Alkylation.- V. References.- 6 Effects on DNA: Transforming Principle.- I. Introduction.- II. Biological Systems.- III. Mutagenesis.- A. Kinetics of Mutagenesis.- B. Specificity of Mutagens.- IV. Measuring Mutagenesis.- A. Antibiotic-Resistant Mutants.- B. Reversion of Nutritional Auxotrophs.- C. Use of Closely Linked Genes.- V. Discussion.- VI. Summary Statement.- VII. Experimental Methods.- A. Preparation of Transforming DNA.- B. Biological Assays.- C. Denaturation of DNA.- D. Renaturation of Denatured DNA.- E. Determining the Base Changes in Mutants and Mutations in Transforming DNA.- VIII. Acknowledgments.- IX. References.- 7 Mutagen Screening with Virulent Bacteriophages.- I. Introduction.- II. Bacteriophages as Genetic Systems.- III. Measuring Viral Mutation Rates.- IV. Mutational Pathways.- V. Bacteriophage Screening Systems.- VI. Conclusions.- VII. References.- 8 Prophage Induction in Lysogenic Bacteria as a Method of Detecting Potential Mutagenic, Carcinogenic, Carcinostatic, and Teratogenic Agents.- I. Introduction.- II. General Properties of Lysogenic Bacteria.- III. Induction of Phage Production in Lysogenic Bacteria and Breakdown of the Lysogenic State.- IV. Experimental Prophage Induction Techniques.- A. Inducible Lysogenic Systems.- B. Prophage Induction Assay Techniques.- C. Paper Chromatographic Techniques.- V. Known Prophage Inducing Agents.- A. Historical.- B. Association of Prophage Inducing Capability with Mutagenic, Carcinogenic, Carcinostatic, and Teratogenic Activities.- VI. Prophage Inducing Agents Present in the Human Environment.- VII. Conclusions.- VIII. References.- 9 The Detection of Chemical Mutagens with Enteric Bacteria.- I. Introduction.- II. Discussion.- A. Advantages of Using Bacterial Test Systems for the Detection of Mutagens.- B. Validity of the Bacterial System as a Test for Mutagens and Carcinogens for Humans.- C. Validity of a Negative Result in the Bacterial Test System.- D. Tester Strains.- E. A General Test for Mutagenesis.- F. Agents That Have Been Shown to Be Mutagenic Using These Strains.- G. Phenotypic Curing.- H. Testing of Compounds, Availability of Strains, and Improvements of Procedures.- III. General Methods.- A. Growth of Bacterial Cultures.- B. Pour Plates for Testing Mutagens.- IV. Acknowledgments.- V. References.- Addendum to Chapter 9 Mutagenesis Studies with Escherichia coli Mutants with Known Amino Acid (and Base-Pair) Changes.- I. Introduction.- II. Mutants with Amino Acid Changes in the Tryptophan Synthetase ? Subunit (A Protein).- A. Mutants with Changes at Position 48.- B. Mutants with Changes at Position 210.- C. Mutants with Changes at Position 233.- D. Other Information.- III. References.- 10 Mutation Induction in Yeast.- I. Introduction.- II. General Description of the Organisms.- III. Mutation.- A. Induction and Isolation of Forward Mutants.- B. Characterization of Forward Mutants.- C. Reverse Mutations, Suppressors, and Resistance Mutations.- IV. Mitotic Segregation.- A. Relevance to Mutagen Studies.- B. Detection of Mitotic Segregation.- C. Genetic and Molecular Mechanisms.- D. Experimental Systems for Studying Mitotic Segregation.- E. Relationship Between Reciprocal and Nonreciprocal Mitotic Segregation.- V. Acknowledgments.- VI. References.- Author Index.