Mutagenicity

Contents

List of Contributors

Preface


1 Screening Chemicals for Mutagenicity: Practices and Pitfalls

I. Introduction

II. Test Batteries

III. Possible Basis of Divergent Assay Responses Observed between Assay Systems

IV. Design, Validation, and Use of Test Batteries

V. Pitfalls in the Use of Mutation Assays

VI. Mutagenic Synergism and Protection

VII. Genotoxic Threshold Dose Levels

VIII. Conclusions

References


2 Qualitative and Quantitative Comparisons between Mutagenic and Carcinogenic Activities of Chemicals

I. Introduction: Environmental Chemicals in Human Carcinogenesis and the Role of Experimental Data in the Assessment of Risk

II. Comparison between Data on Carcinogenicity in Humans and Results of Mutagenicity and Other Short-Term Tests

III. Comparisons between Data from Long-Term Animal Carcinogenicity Tests and Results of Mutagenicity (Short-Term) Tests

IV. Quantitative Correlations between the Carcinogenic Potency of Chemicals and Their Mutagenic Activity

V. Comparison of the in Vitro Mutagenicity and the in Vivo Covalent Binding Index of Chemical Carcinogens

VI. Factors That May Affect the Activity of Carcinogenic Chemicals in Short-Term Tests and in Experimental Animals

VII. Conclusions

References


3 The Use of Mutagenicity to Evaluate Carcinogenic Hazards in Our Daily Lives

I. Introduction

II. Experimental Studies

III. Conclusions and Future Studies

References


4 Mutagenicity and Lung Cancer in a Steel Foundry Environment

I. Introduction

II. Foundry Mutagenicity Study

III. Results

IV. Conclusions and Discussion

References


5 The Use of Mutagenicity Testing to Evaluate Food Products

I. Introduction

II. Methodology

III. Mutagens in Nonprocessed Food

IV. Mutagens Formed during Food Preparation and Cooking

V. Model Browning Reactions

VI. Integrated Mutagenic Load of Diets

VII. Outlook

References


6 Transformation of Somatic Cells in Culture

I. Introduction

II. In Vitro and in Vivo Studies of Basic Mechanisms of Neoplastic Transformation

III. Types of Cell Transformation Systems

IV. Regulatory and Commercial Uses of Neoplastic Transformation Assays

V. Summary

References


7 Mutagenicity Testing with Cultured Mammalian Cells: Cytogenetic Assays

I. Introduction

II. Cytological End Points Used

III. Methodology

IV. Comparison between Chromosome Aberrations and Sister Chromatid Exchanges

V. Types of Lesions Leading to Sister Chromatid Exchanges and/or Chromosomal Aberrations

VI. Influence of Tumor Promoters or Inhibitors on Induction of Chromosomal Alterations

VII. Chromosomal Alterations and Point Mutations

VIII. Mutagenic Compounds Assayed by Cytogenetic Methods

IX. Detection of Carcinogens

X. Application of Cytogenetic Tests to Detect Human Recessive Disorders

XI. Detection of Complementation Groups of Recessive Disorders

XII. Effect of Cocultivation of Two Different Types of Cells

XIII. Quantification of the Biological Effects in Relation to Primary Effects in the DNA

XIV. In Vitro Cytogenetic Assays to Detect Mutagens in Comparison to Other Short-Term Tests

XV. The Human Lymphocyte

References


8 Measurement of Mutations in Somatic Cells in Culture

I. Importance of Using Mammalian Cells in Culture for Mutagenesis Studies

II. Overview of Selected Aspects of Mammalian Cell Mutagenesis Studies

III. Utilization of Mutagenesis Studies with Cultured Mammalian Cells

IV. Conclusion

References


9 Chromosomal Aberrations Induced in Occupationally Exposed Persons

I. Introduction: Possibilities Offered by Cytogenetic Methods for Testing the Effects of Small Doses of Chemicals Applied Chronically to Man

II. Studies of Workers Occupationally Exposed to Chemicals

III. Open Questions in the Field of Cytogenetic Monitoring of Occupationally Exposed People

IV. Conclusions: Summary of Current Knowledge and Future Trends

References


10 The Rationale and Methodology for Quantifying Sister Chromatid Exchange in Humans

I. Rationale for the Analysis of Sister Chromatid Exchange in Humans

II. Methodological Aspects of Sister Chromatid Exchange Analysis in Human Populations

III. Statistical Considerations

IV. Application to Human Studies

References


11 The 6-Thioguanine-Resistant Peripheral Blood Lymphocyte Assay for Direct Mutagenicity Testing in Humans

I. Introduction

II. The Thioguanine-Resistant (TGr) PBL Assay Method

III. Sample Results

IV. Statistical Analysis Methods

V. Discussion

References


12 Sperm Assays as Indicators of Chemically Induced Germ-Cell Damage in Man

I. Introduction

II. Description of Available Human Sperm Assays and Their Relative Sensitivities

III. Review of the Uses of Sperm Assays in Chemically Exposed Men

IV. Rationale, Strategies, and Problems Encountered in the Use of Human Sperm Assays in Exposed Populations

V. The Implications of Chemically Induced Sperm Changes

VI. Conclusions

References


13 Cytogenetic Events in Vivo

I. Introduction

II. Structural Chromosome Aberrations

III. Sister Chromatid Exchanges (SCEs)

References


14 Dominant Skeletal Mutations: Applications in Mutagenicity Testing and Risk Estimation

I. Introduction

II. Dominant Skeletal Mutation Rate Experiment Using Breeding Tests

III. The New Sensitive-Indicator Method

IV. Other Major Questions about Genetic Risk Now Amenable to Study

V. Study of Induced Dominant Damage to Other Body Systems

VI. Effects of Decreased Viability and Incomplete Penetrance on Experimental Frequencies of Induced Dominant

Damage

VII. Relative Merits of Sensitive-Indicator and Standard Specific-Locus Methods

VIII. Special Case in Which Risk Estimation Is Greatly Simplified by Using Sensitive-Indicator and Specific-Locus Methods

References


15 Plants as Sensitive in Situ Detectors of Atmospheric Mutagens

I. Introduction

II. Tradescantia as an in Situ System for the Detection of Atmospheric Mutagens

III. Pollen Systems for the Detection of Atmospheric Mutagens

IV. Other Higher-Plant Mutagen Assay Systems

V. The Use of in Situ Weed Communities for the Detection of Atmospheric Mutagens

VI. Discussion and Conclusions

References


16 Fishes as Biological Detectors of the Effects of Genotoxic Agents

I. Introduction

II. Methodologies for Aquatic Genetic Toxicology

III. Summary and Conclusions

References

Index