New developments in the study of environmental mutagens continue to evolve in this rapidly emerging field. In Volume 7 of Chemical Mutagens, we have focused on various new techniques for the detection of genetic damage in somatic cells and germ cells of mammals and the use of lower eukaryotic microorganisms to detect aneuploidy as well as other types of genetic damage. Attention has also been given to the role of in vitro metabolic activation as a mechanism for modifying the genetic effects of different environmental chemicals. In a chapter on compar­ ative mutagenesis, reaction kinetics and their relationship to the mu­ tagenic action of monofunctional alkylating agents in higher eukaryotic organisms are examined. In another chapter, the pharmacology and toxicology of nitrites and nitrates, which are in widespread distribution in the environment, are discussed in detail. The books in this series have provided a mechanism for the publication of many important new developments in the study of the genetic effects of environmental chemicals. This series was launched by Dr. Alexander Hollaender who, beginning in 1971, edited Volumes 1-4 and then coedited Volumes 5-7. The success of his lO-year effort with these volumes is another testimony to Dr. Hollaender's many contri­ butions to the field of environmental mutagenesis. As Dr.

1 Effects of Chemicals on Chromosome-Aberration Production in Male and Female Germ Cells.- 1. Introduction.- 2. Methods of Detecting Chromosome Aberrations Induced in Germ Cells.- 3. Male Germ Cells.- 3.1. Preparation Techniques.- 3.2. Chromosome Studies of Spermatogonial Mitoses.- 3.3. Chromosome Analysis in Spermatocytes after Treatment of Stem-Cell Spermatogonia.- 3.4. Chromosome Analysis in Spermatocytes after Treatment of Meiotic Prophase Stages.- 3.5. Analysis of Cleavage Stages after Treatment of Meiotic and Postmeiotic Male Germ Cells.- 4. Female Germ Cells.- 4.1. Preparation Techniques.- 4.2. Analysis of Chromosome-Aberration Induction in Oocytes.- 5. Interpretations and Conclusions.- 6. References.- 2 The Use of Immunological Techniques to Detect Cells of Rare Genotype.- 1. Introduction.- 2. Isolation of Antibodies Suitable for Detecting Mutants: Antibodies to Single and Multiple Amino Acid Differences in Proteins.- 2.1. General.- 2.2. Isolation Procedures and Examples.- 2.3. Detection of Monospecific Antibody in the Serum.- 3. Detection of Mutants with the Help of Antibodies.- 3.1. Hemoglobin System.- 3.2. Lactate Dehydrogenase-X System.- 3.3. Immunoglobulin-Allotype System.- 3.4. H-2 System.- 4. Conclusion.- 5. References.- 3 Metabolic Activation Systems in Vitro for Carcinogen/Mutagen Screening Tests.- 1. Introduction.- 2. Common Pathways for the Activation and Detoxification of Carcinogens/Mutagens.- 2.1. Enzymatic Activation Reactions That Introduce or Modify Functional Groups (Phase I Reactions).- 2.2. Enzymatic Conjugation (Phase II Reactions).- 2.3. Detoxification Reactions of Carcinogens/Mutagens.- 3. Subcellular Metabolic Activation Systems: Some General Remarks.- 3.1. Hepatic Postmitochondrial Supernatant (S-9) Fraction from Rats.- 3.2. Purified Subcellular Hepatic-Tissue Fractions (Enzymes) from Rat Liver and Other Sources.- 3.3. Species Variations in Hepatic Metabolic Activation Reactions.- 3.4. Metabolic Activation by Rodent Extrahepatic-Tissue Fractions.- 3.5. Carcinogen/Mutagen Activation by Human Liver (or Other Tissue) Enzymes.- 4. Cellular Metabolic Activation Systems.- 4.1. Cultured Cells That Possess Metabolic Activity.- 4.2. Assays That Use Cultured Mammalian Cells for Metabolic Activation.- 4.3. Evaluation of the Efficiency of Carcinogen/Mutagen Screening Tests That Use Intact Mammalian Cells for Metabolic Activation.- 5. Combination of in Vivo-in Vitro Screening Tests of Carcinogens/Mutagens: Recent Developments.- 6. Problems in the Extrapolation of Data Obtained in Vitro to the Intact Mammalian Organism.- 7. Conclusions.- 8. References.- 4 Microbial Metabolism of Environmental Chemicals to Mutagens and Carcinogens.- 1. Introduction.- 2. Definition of a Compound as a Promutagen.- 3. Chemicals That Can Be Activated to Environmental Mutagens and Carcinogens by Microorganisms.- 3.1. Azo Dyes.- 3.2. Glycosidase Conjugates.- 3.3. Nitroaryl and Heterocyclic Compounds.- 3.4. N-Hydroxy Aromatic Amides and Amines.- 3.5. Chemicals That Require Activation by Cytochrome-P-450-Dependent Monooxygenases.- 3.6. Ethidium Bromide.- 4. Role of the Intestinal Microflora in the Formation of Mutagens and Carcinogens.- 5. Short-Term Test Systems and the Role of Microorganisms in the Metabolism of Chemicals into Mutagens: Conclusions.- 5.1. Metabolic Systems of Indicator Organisms.- 5.2. Activation by Intestinal Microbial Flora and Short-Term Test Systems.- 6. Summary.- 7. References.- 5 Short-Term Tests for Chemicals That Promote Aneuploidy.- 1. Introduction.- 2. Test Systems.- 2.1. Meiotic Systems.- 2.2. Mitotic Systems.- 3. Discussion.- 3.1. Biological Relevance.- 3.2. Application.- 4. References.- 6 Nitrates and Nitrites: Ingestion, Pharmacodynamics, and Toxicology.- 1. Introduction.- 2. Major Sources of Human Exposure.- 2.1. Ingestion.- 2.2. Endogenous Synthesis.- 3. Flow in Humans.- 3.1. Ingestion and Endogenous Synthesis.- 3.2. Active Nitrate Transport from the Gastrointestinal Lumen.- 3.3. Plasma Levels of Pertinent Anions.- 3.4. Tissue Compartments and Nitrate Storage.- 3.5. Salivary Recirculation of Nitrate.- 3.6. Gastric Recirculation of Nitrate.- 3.7. Mammary Transport of Nitrate.- 3.8. Placental Transport of Nitrate.- 3.9. Nitrate and Nitrite Loss in Vivo.- 3.10. Nitrate in Human Urine.- 4. Suspected Health Consequences.- 4.1. Nitrate Ingestion: Tolerance to Acute Effects.- 4.2. Nitrate Ingestion: Possible Long-Term Effects.- 4.3. Ingestion and in Vivo Production of Nitrite.- 5. Reduction of Exposure.- 5.1. Cured Meats.- 5.2. Vegetables.- 5.3. Water.- 6. Summary.- 7. References.- 7 The Relation between Reaction Kinetics and Mutagenic Action of Monofunctional Alkylating Agents in Higher Eukaryotic Systems: Interspecies Comparisons.- 1. Introduction.- 2. Mechanism of Action of Alkylating Agents.- 3. Reaction of Alkylating Agents with DNA and Proteins.- 3.1. Alkylalkanesulfonates.- 3.2. Dialkylsulfates.- 3.3. Dialkylnitrosamines, Alkylnitrosamides, and Alkylnitrosoguanidines.- 3.4. Comparison of Reactivity.- 3.5. Significance of Alkyl Groups in DNA.- 4. Response to Alkylating Agents.- 4.1. Higher Plants.- 4.2. Drosophila.- 4.3. Mammals.- 5. Interspecies Comparisons.- 5.1. Effectiveness.- 5.2. Efficiency.- 5.3. Carcinogenicity.- 5.4. Problems for Future Work.- 6. Conclusions.- 7. References.- 8 The Human Leukocyte Test System.- 1. Introduction.- 2. Some Early Events during Human Leukocyte Stimulation...- 3. DNA Synthesis, Mitosis, and the Diversity of the Culture System.- 4. Differences in Mutagen Sensitivity of Leukocyte Subpopulations?.- 5. Fate of Chromosomal Damage during Successive Cell Cycles.- 6. Selected Examples of in Vivo Investigations with Human Leukocytes.- 6.1. Alcohol and Tobacco Smoke.- 6.2. Psychotropic Drugs.- 6.3. Illicit Drugs.- 6.4. Antiepileptic Drugs.- 7. Appendix: Standard Protocol for Human Leukocyte Culture Preparation.- 7.1. Contents of a Standard Leukocyte Culture.- 7.2. Preparation of Cultures.- 7.3. Preparation of Slides.- 7.4. 5-Bromodeoxyuridine-Labeling.- 7.5. A Note on Centromeric Sister-Chromatid Exchanges.- 8. References.- 9 The Activation of Chemicals into Mutagens by Green Plants.- 1. Introduction.- 2. Plant Activation of Promutagens.- 2.1. In Vivo Plant Activation.- 2.2. In Vitro Plant Activation.- 3. Deactivation of Mutagens by Plants.- 4. Response of Plant Genetic Assays to Known Mammalian Promutagens.- 4.1. Nitrosamines.- 4.2. s-Triazines.- 4.3. Maleic Hydrazide.- 4.4. Other Promutagens.- 5. Conclusion.- 6. References.- 10 Unscheduled DNA Synthesis in Mammalian Germ Cells-Its Potential Use in Mutagenicity Testing Gary A. Sega.- 1…