Chemical Carcinogenesis and Mutagenesis I

ISBN-13: 9783642747779 / Angielski / Miękka / 2011 / 604 str.

F. a. Beland; L. G. Cain; J. S. Felton

Opis

I have been privileged to witness and participate in the great growth of knowledge on chemical carcinogenesis and mutagenesis since 1939 when I entered graduate school in biochemistry at the University of Wisconsin- Madison. I immediately started to work with the carcinogenic aminoazo dyes un- der the direction of Professor CARL BAUMANN. In 1942 I joined a fellow graduate student, ELIZABE1H CAVERT, in marriage and we soon commenced a joyous part- nership in research on chemical carcinogenesis at the McArdle Laboratory for Cancer Research in the University of Wisconsin Medical School in Madison. This collaboration lasted 45 years. I am very grateful that this volume is dedi- cated to the memory of Elizabeth. The important and varied topics that are reviewed here attest to the continued growth of the fields of chemical car- cinogenesis and mutagenesis, including their recent and fruitful union with viral oncology. I feel very optimistic about the application of knowledge in these fields to the eventual solution of numerous problems, including the detection and estimation of the risks to humans of environmental chemical carcinogens and re- lated factors.

Spis treści

I. Theories of Carcinogenesis.- 1 Mechanisms of Chemical Carcinogenesis: Theoretical and Experimental Bases.- A. Introduction.- B. Historical Aspects.- C. Mechanistic Theories of Chemical Carcinogenesis.- I. Electrophilicity of Chemicals as a Determinant of Their Carcinogenicity.- II. Potential Role of Free Radicals as Ultimate Carcinogens.- III. Altered DNA Methylation as a Theoretical Mechanism of Chemical Carcinogenesis.- IV. Aberrations of DNA Repair as Theoretical Mechanisms of Chemical Carcinogenesis.- V. Other Theoretical Mechanisms of Chemical Carcinogenesis.- D. Pathogenesis of Malignancy: Natural History of Neoplastic Development.- I. Initiation.- II. Promotion.- III. Progression.- E. Reconciliation of the Theoretical Bases of Chemical Carcinogenesis with the Natural History of Neoplastic Development.- F. Conclusions.- References.- II. Exposure to Chemical Carcinogens.- 2 Environmental Carcinogens.- A. Introduction.- B. Fate of Chemicals in the Environment.- C. Classification of Environmental Carcinogens.- D. Exposed Populations.- E. Risk Assessment.- F. Examples of Important Environmental Carcinogens.- I. Arsenic.- II. Cadmium.- III. Chromium.- IV. Nickel.- V. Asbestos.- VI. Acrylonitrile.- VII. Benzene.- VIII. 1,2-Dichloroethane.- IX. Formaldehyde.- X. Methylene Chloride (Dichloromethane).- XI. Polycyclic Aromatic Hydrocarbons and Nitrated Forms.- XII. Polyhalogenated Aromatic Compounds.- 1. Polychlorinated Biphenyls.- 2. Chlorinated Phenols.- 3. Hexachlorobenzene.- 4. Dichlorodiphenyltrichloroethane, Toxaphene and Chlordane.- XIII. Radon.- XIV. Styrene.- XV. Tetrachloroethylene.- XVI. Trihalomethanes.- XVII. Vinyl Chloride.- G. Conclusions.- References.- 3 Advances in Tobacco Carcinogenesis.- A. Introduction.- B. Tobacco and Tobacco Smoke.- C. The Changing Cigarette.- D. Carcinogenic Compounds in Tobacco and Tobacco Smoke.- I. Polynuclear Aromatic Hydrocarbons (PAH).- II. N-Nitrosamines.- III. Aromatic Amines.- IV. Aldehydes.- V. Miscellaneous Organic Compounds.- VI. Inorganic Carcinogens.- E. Smokeless Tobacco.- I. Epidemiology.- II. Bioassays.- III. Carcinogens.- F. Environmental Tobacco Smoke.- G. Recent Studies on Mechanisms of Tobacco Carcinogenesis and Their Application to Dosimetry.- I. Polynuclear Aromatic Hydrocarbons.- II. Tobacco-Specific N-Nitrosamines.- III. Aromatic Amines.- IV. DNA Damage Induced by Unknown Constituents of Tobacco Smoke.- H. Perspectives.- I. Inhalation Bioassays.- II. Flavor Additives.- III. Bioassays with Smokeless Tobacco.- IV. Nutrition and Tobacco Carcinogenesis.- V. Tobacco Smoke and Indoor Radon Levels.- VI. Biochemistry of Tobacco Carcinogenesis.- References.- 4 Occupational Carcinogens.- A. Historical Introduction.- I. Early Occupational Cancer.- II. Prevention of Occupational Cancer.- III. Occupational Carcinogens.- B. Polycyclic Aromatic Hydrocarbons.- I. Occupational Skin and Scrotal Cancer.- II. Cancer at Other Sites.- III. Recognition and Occurrence of Polycyclic Hydrocarbons.- C. Aromatic Amines and Related Compounds.- I. Occupational Bladder Cancer.- II. Recognition of Human Bladder Carcinogens.- III. Control of Amine Carcinogen Hazards.- IV. Other 2-and 3-Ring Aromatic Amines.- 1. Substituted Benzidines and Other Industrial Compounds.- 2. 2-Fluorenylacetamide.- V. Single-Ring Aromatic Amines.- 1. Aniline and Derivatives.- 2. Phenylenediamines.- VI. Dyes.- 1. Magenta and Auramine.- 2. Azo Dyes.- VII. Nitro Compounds.- D. Alkylating Agents.- I. Mustard Gas; 2,2’-Bis(chloroethyl) Sulphide.- II. Chloromethyl Ethers.- III. Benzoyl Chloride Manufacture.- IV. Isopropanol Manufacture and Alkyl Sulphates.- V. Epoxides.- 1. Ethylene Oxide.- 2. Other Epoxides.- VI. ?-Propiolactone.- VII. Aziridines.- E. Halocarbons.- I. Vinyl Chloride.- II. Vinylidene Chloride and Chloroprene.- III. 1, 2-Dibromoethane and Related Compounds.- IV. Tetraehloromethane.- V. Other Chlorinated Solvents.- VI. Polychlorinated Pesticides.- VII. Polychlorinated and Polybrominated Biphenyls.- F. Nitrosamines.- I. Nitrosamines in Industry.- 1. Intentional Use.- 2. Inadvertent Formation.- G. Inorganic Carcinogens.- I. Arsenic.- II. Nickel.- III. Chromium.- IV. Beryllium.- V. Cadmium.- VI. Iron.- VII. Other Metals.- H. Asbestos and Other Mineral Fibres.- I. Introduction.- II. Asbestos and Lung Cancer.- 1. Synergism with Smoking.- III. Asbestos and Mesothelioma.- 1. Erionite and Mesothelioma.- IV. Asbestos and Other Cancers.- V. Asbestos Controls.- VI. Man-Made Mineral Fibres.- I. Wood and Leather Dust.- I. Nasal Cancer in Woodworkers.- II. Nasal Cancer in Leather Workers.- J. Benzene.- K. Formaldehyde and Other Aldehydees.- I. Animal Bioassays.- II. Epidemiological Studies.- III. Other Aldehydes.- L. Some Other Suspected Occupational Hazards.- I. Acrylonitrile.- II. Acrylamide.- III. Amitrole.- IV. 1,3-Butadiene.- V. Hydrazine.- VI. Di(2-ethylhexyl)/Phthalate and Related Compounds.- VII. Tobacco Smoke.- M. Continuing Problems and Prospects.- I. Proportion of Cancer Attributable to Occupation.- II. Identification of Carcinogenic Hazards.- 1. Identification Through Epidemiology.- 2. Experimental Identification of Carcinogens.- References.- 5 Therapeutic Agents as Potential Carcinogens.- A. Introduction.- B. Classification of Potentially Carcinogenic Therapeutic Agents.- C. Carcinogenicity of Antineoplastic Agents.- I. Nitrogen Mustards.- II. Myleran.- III. Therapeutic Nitrosoureas.- IV. Thiotepa.- V. Procarbazine and Dacarbazine.- VI. Summary.- D. Hormones as Carcinogenic Agents.- E. Other Therapeutic Agents as Potential Carcinogens.- F. Conclusions.- References.- III. In Vivo and In Vitro Carcinogenesis.- 6 In Vivo Testing for Carcinogenicity.- A. Introduction.- B. Development and Use of In Vivo Carcinogenesis Tests.- I. History of Carcinogenicity Testing.- II. The Bioassay Program (National Cancer Institute).- III. Mechanisms of Carcinogenesis.- IV. Carcinogenesis as a Toxicity Test.- V. Short-Term Assays as Substitutes for In Vivo Carcinogenesis.- VI. In Vivo Assays with N-Nitroso Compounds as Examples.- VII. Methods of In Vivo Carcinogenesis.- VIII. Routes of Administration.- IX. Assessment of Results.- C. Criteria for In Vivo Assays.- I. Group Size.- II. Species and Sex.- III. Route of Administration.- 1. Oral.- 2. Skin Painting.- 3. Inhalation.- 4. Conclusions.- IV. Size of Dose and Dose Selection.- 1. Studies in Adults.- 2. Multigeneration Studies.- V. Conduct of the Experiment.- VI. Examination of Animals and Evaluation of Results.- D. Conclusions.- References.- 7 Transformation of Cells in Culture.- A. Introduction.- B. Definition of Terms.- C. Transformation of Rodent Mesenchymal Cells.- I. Cells with a Limited Lifespan.- II. Established Cell Lines.- III. Oncogenes and the Transformation of Rodent Mesenchymal Cells.- 1. Introduction of Genetic Material into Mammalian Cells.- 2. Transformation of Immortal Fibroblasts by Oncogenes.- 3. Transformation of Primary Cells.- IV. Role of Immortalisation in Transformation.- D. Transformation of Rodent Epithelial Cells.- I. Submandibular Gland.- 1. Phenotypic Stages.- 2. Effect of a Tumor Promoter.- 3. Analysis of DNA Content and Karyotypic Markers.- II. Bladder.- 1. Phenotypic Stages.- 2. Effect of Promoting Agents.- 3. Properties of Immortal and Transformed Cell Lines.- 4. Role of Oncogenes and Suppressor Genes.- III. Trachea.- 1. Phenotypic Stages.- 2. Promotion and Inhibition.- 3. Role of Oncogenes.- IV. Epidermis.- 1. Induction of Foci Resistant to Calcium-Induced Differentiation.- 2. Effect of TPA.- 3. Role of ras Oncogenes.- V. Discussion.- E. Transformation of Human Cells.- I. Differences Between Human and Rodent Cells.- II. Transformation of Human Mesenchymal Cells.- III. Transformation of Human Epithelial Cells.- F. Conclusions.- References.- IV. Reactions of Carcinogens with DNA.- 8 Metabolic Activation and DNA Adducts of Aromatic Amines and Nitroaromatic Hydrocarbons.- A. Introduction.- I. 1-Naphthylamine and 1-Nitronaphthalene.- II. 2-Naphthylamine and 2-Nitronaphthalene.- III. 4-Aminobiphenyl and Derivatives.- IV. 2-Acetylaminofluorene, 2-Aminofluorene, and 2-Nitrofluorene.- IV. Benzidine.- VI.N,N-Dimethyl-4-aminoazobenzene and Its Demethylated Derivatives.- VII. 2-Acetylaminophenanthrene.- VIII. 4-Acetylaminostilbene.- IX. Nitropyrenes.- X. 6-Aminochrysene and 6-Nitrochrysene.- XI. Heterocyclic Aromatic Amines.- B. Conclusions and Comments.- References.- 9 Polycyclic Aromatic Hydrocarbons: Metabolism, Activation and Tumour Initiation.- A. Introduction.- B. Metabolism.- I. Diols.- II. Phenols.- III. Conjugation with Glutathione.- IV. Conjugation with Glucuronic and Sulphuric Acids.- V. Hydroxylated Products - Further Metabolism.- VI. Mechanisms Involved in Metabolic Activation.- C. Pathways of Activation.- I. 7,12-Dimethylbenz[a]antracene.- II. Benzo[a]pyrene.- III. Dibenzo[a,e]fluoranthene.- IV. Dibenz[a,h] anthracene.- V. Benz[c]aeridine.- VI. Benz[a]anthracene and Chrysene.- D. Stereochemistry of Activation Pathways.- I. Benzo[a]pyrene.- II. Primary Metabolism.- III. Secondary Metabolism.- E. Factors Governing Susceptibility to PAH-Induced Tumorigenesis.- I. Species and Strain Differences.- 1. Metabolism.- 2. Formation and Persistence of DNA Adducts.- II. Tissue Differences.- III. Influence of Sex and Age.- F. Concluding Remarks.- References.- 10 Interactions of Fungal and Plant Toxins with DNA: Aflatoxins, Sterigmatocystin, Safrole, Cycasin, and Pyrrolizidine Alkaloids.- A. Introduction.- B. Aflatoxins.- I. Occurrence.- II. Aflatoxin Chemistry, Metabolism, DNA and Protein Adduct Formation.- III. Experimental Animal Models for Aflatoxin Carcinogenesis.- 1. Animal Models, Dietary Antioxidants, and DNA Adduct Formation.- 2. Interactions with Cellular Oncogenes.- IV. Affinity Chromatography for Aflatoxin-DNA Adducts and Other Metabolite Isolation from Biological Samples.- V. Human Liver Cancer and Aflatoxin: Epidemiology and Exposure Monitoring.- C. Sterigmatocystin.- D. Safrole and Related Compounds.- I. Carcinogenicity.- II. DNA Adduct Formation and Oncogene Interactions.- E. Cycasin.- F. Pyrrolizidine Alkaloids.- G. Summary.- References.- 11 N-Nitroso Compounds.- A. Introduction: Development of the Importance of N-Nitroso Compounds for Carcinogenesis Studies.- I. Historical Origins.- II. Development of the Concept that N-Nitroso Compounds are Alkylating Carcinogens.- III. N-Nitroso Compounds as Mutagenic Carcinogens.- IV. N-Nitroso Compounds as Mutagenic Activators of Oncogenes.- B. Organotropism in Carcinogenesis by N-Nitroso Compounds.- I. Role of N-Nitroso Compounds in Multistage Carcinogenesis.- II. Structure-Activity Relationships for N-Nitroso Compounds.- III. Role of Metabolic Activation in Structure-Activity Relationships.- C. N-Nitroso Compounds and Human Cancer.- I. Introduction.- II. Environmental and Endogenous Formation of N-Nitroso Compounds.- III. In Vivo Alkylating as a Measure of Human Exposure.- IV. Activating Mutations in Human Tumour Oncogenes Possibly Consistent with Induction by N-Nitroso Compounds.- D. Epidemiology.- E. Conclusions.- References.- 12 Heterocyclic-Amine Mutagens/Carcinogens in Foods.- A. Introduction.- B. Chemical Analysis of Heterocyclic-Amine-Mutagens in Cooked Foods.- I. Food Mutagen Sources and Exposure.- II. Chemical Extraction and Purification.- 1. Extraction.- 2. Bioassay-Directed Purification.- III. Identification of Unknown Mutagens.- 1. General Approach.- 2. Characteristics of Food Mutagens.- C. Mutagen Formation from Modeling Reactions.- D. Heavy Isotope Labeling of Mutagens in Model Reactions.- E. Structure and Mutagenicity of the Aminoimidazoazaarene Compounds.- F. Genetic Toxicology.- I. Microbial.- II. Nonmicrobial Genotoxicity.- 1. Mutation.- 2. DNA Repair and Damage.- 3. Clastogenesis.- G. DNA Binding.- I. Guanine Adduets.- II. Adduet Analysis by 32P-Postlabelling.- H. Carcinogenesis.- J. Significance of Aminoimidazoazaarenes in the Diet.- References.- 13 Modem Methods of DNA Adduct Determination.- A. Introduction.- B. Postlabelling Methods.- I. Principles of 32P-Postlabelling.- II. Applications in Animal and Tissue Culture Studies.- III. Exposure to Environmental Carcinogens: Animal & Human Studies.- IV. Advantages and Limitations of 32P-Postlabelling.- V. 14C-Postlabelling.- VI. Fluorescent Postlabelling.- C. Immunochemical Methods.- I. Principles.- II. Applications in Animal and Tissue Culture Studies.- III. Human Studies.- IV. Advantages and Limitations of Immunochemical Methods.- D. Physicochemical Methods.- I. Fluorescence Spectroscopy.- II. Gas Chromatography and Mass Spectrometry.- E. Future Prospects.- References.- 14 Biological Consequences of Reactions with DNA: Role of Specific Lesions.- A. Introduction.- B. Biological Effects.- I. Effects on the Synthesis of Macromolecules.- II. Promutagenicity and Alkylation-Induced Mutagenesis.- III. Clastogenesis.- IV. Teratogenesis and Transplacental Effects.- V. Transformation in Cultured Mammalian Cells.- C. Correlation of Promutagenic Lesions with Carcinogenesis.- D. Role of Specific Lesions: Effects of E. coli Alkyltransferase Gene Expression in Mammalian Cells.- I. Mutagenesis.- II. Sister Chromatid Exchanges and Other Clastogenic Events.- III. Toxicity.- E. Conclusions.- References.