Genotoxicology of N-Nitroso Compounds, Softcover reprint of the original 1st ed. 1984 Topics in Chemical Mutagenesis Series

Toph's in Chemical Mutagenesis is a new series dedicated to studies in the areas of environmental chemical mutagenesis and genetic toxicology. In this series we will explore some of many topics that are emerging in these rapidly developing fields. The purpose of the present volume is to attempt to organize and compare the genotoxic properties of the N-nitroso compounds. This is a particularly interesting class of compounds because of the problems encountered with the Salmonella assay of Ames in generating both false positive and false negative results. The battery approach using a number of assay systems seems more appropriate to evaluate chemicals in this class. Topics to be discussed in other volumes in this series include single-cell mutation monitoring systems, the detection of genetic damage in mammalian germ cells, the mutagenicity of pesticides, problems in monitoring human populations in genetic toxicology, and a glossary of terms in genetic toxicology. All of these books are in various stages of development and should appear within the next few years. Frederick J. de Serres Series Editor vii Preface During the past ten years there has been an explosive development in the number of short-term tests to predict the biological risks, especially risks of cancer, in exposure to xenobiotic chemicals. The number of published articles in this area has reached many thousands a year and there are several new journals devoted almost entirely to the presentation of the results obtained in these tests.

1. Formation of N-Nitroso Compounds and Their Significance.- 2. N-Nitrosamine Mutagenicity Using the Salmonella/Mammalian-Microsome Mutagenicity Assay.- 1. Introduction.- 2. Materials and Methods.- 3. Mutagenic Activity and Chemical Structure.- 4. Conclusions / Discussion.- 5. References.- 3. Structural Basis for Mutagenic Activity of N-Nitrosamines in the Salmonella Histidine Reversion Assay.- 1. Introduction.- 2. Salmonella typhimurium—Histidine Reversion Assay.- 3. Mutagenesis Studies in Salmonella typhimurium.- 4. References.- 4. Effects of pH and Structure on the Mutagenic Activity of N-Nitroso Compounds.- 1. Introduction.- 2. Methods.- 3. Effects of pH on Mutagenesis and DNA Alkylation by N-Nitroso Compounds.- 4. Mutagenesis by N-Nitroso-N’-nitroso-N-alkylguanidines.- 5. Repair of O6-Methylguanine and Its Effect on Mutagenesis.- 6. Alternate Mechanisms of Mutagenesis by N-Nitroso Compounds.- 7. Mutagenesis by a Series of “Weakly Mutagenic” N-Nitrosamines: Effects of Structure.- 8. Correlation between Mutagenic Potencies and Carcinogenic Activities of Some N-Nitroso Compounds.- 9. References.- 5. Induction of Bacteriophage Lambda by N-Nitroso Compounds.- 1. Mechanism of Induction.- 2. Genetics and Methodology.- 3. Factors Affecting Induction by Nitroso Compounds.- 4. Structure-Activity Relationships.- 5. Relationships between Mutagenicity, Carcinogenicity, and Phage Induction.- 6. Mechanism of Action of Nitroso Compounds as Inducers of Bacteriophage Lambda.- 7. References.- 6. The Relationship between the Carcinogenicity and Mutagenicity of Nitrosamines in a Hepatocyte-Mediated Mutagenicity Assay.- 7. Mutagenic Activity of Nitrosamines in Mammalian Cells: Study with the CHO/HGPRT and Human Leukocyte SCE Assays.- 1. Introduction.- 2. Mutagenic Activity ofEight Nitrosamines in the CHO / HGPRT Assay.- 3. Mutagenic Activity of 15 Nitrosamines in the Human Leukocyte SCE Assay.- 4. Summary and Concluding Remarks.- 5. References.- 8. Dimethylnitrosamine Demethylase and the Mutagenicity of Dimethylnitrosamine: Effects of Rodent Liver Fractions and Dimethylsulfoxide.- 1. Introduction.- 2. Materials and Methods.- 3. Results.- 4. Discussion.- 5. References.- 9. The Relationship between Metabolism and Mutagenicity of Two Cyclic Nitrosamines.- 1. Introduction.- 2. Materials and Methods.- 3. Results and Discussion.- 4. Conclusion.- 5. References.- 10. Structure—Activity Relations in Carcinogenesis by N-Nitroso Compounds.- 1. Introduction.- 2. Nitrosoalkylamides.- 3. Alkylation by Nitrosamines.- 4. Nitrosomethylalkylamines (X).- 5. Substituted Acyclic Nitrosamines.- 6. Cyclic Nitrosamines.- 7. Substituted Cyclic Nitrosamines.- 8. Derivatives of Nitrosopiperidine.- 9. Conclusion.- 10. References.- 11. Comparison of Mutagenic and Carcinogenic Properties: A Critique.- 1. Introduction.- 2. Tabular Summation and Integration of Results.- 3. Comparison of Mutagenic End Points.- 4. Relationship between Short-Term Test Results and Carcinogenicity.- 5. Precautions in Interpretation and Extrapolation.- 6. References.