Chemical Carcinogenesis and Mutagenesis II

ISBN-13: 9783642747809 / Angielski / Miękka / 2011 / 467 str.

Colin S. Cooper; Philip L. Grover

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, ELIZABETH CA VERT, 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. Relationships Between Mutagenesis and Carcinogenesis.- 1 Use of Mutations in Bacteria as Indicators of Carcinogenic Potential.- A. Introduction.- B. Historical Background.- C. Use of Assays.- I. General.- 1. Toxicology Screening.- 2. Research Uses.- II. Limitations.- 1. Metabolic Activation.- 2. Non-Genotoxic Carcinogens.- D. Methods.- I. General Introduction.- II. Outline Protocols for Reverse Mutation Assays.- 1. Plate-and-Treat Assays.- 2. Spot Tests and Gradient-Plate Assays.- 3. Treat-and-Plate Assays.- 4. Fluctuation Tests.- III. Forward Mutation Assays.- IV. Host-Mediated Assays.- E. Use of the Results from Mutation Assays.- I. Basic Meaning of Such Results.- II. Use of the Results.- 1. Extrapolation of the Results.- 2. Toxicological Significance of the Results.- F. Summary and Conclusions.- References.- 2 Mammalian Cell Mutations.- A. Introduction.- B. Genetics and Principles of Experimental Design.- I. Genetics.- II. Experimental Design.- C. Cell Types.- I. Assessment of Mutation in Rodent Cells.- 1. L5178Y Mouse Lymphoma Cells.- 2. Chinese Hamster V79 and CHO Cells.- 3. Mouse Lymphocytes.- II. Human Cells.- 1. Untransformed Fibroblasts.- 2. Transformed Fibroblasts.- 3. Lymphoblastoid Cell Lines.- 4. T Lymphocytes.- 5. Erythrocytes.- D. Use of Recombinant Shuttle Vectors.- I. Integrated Shuttle Vectors.- II. Extrachromosomal Shuttle Vectors.- E. Conclusions.- References.- 3 Mechanisms of Repair in Mammalian Cells.- A. Introduction.- B. Excision Repair.- I. Incision.- II. Excision and Repair Synthesis.- III. Enzymes Possibly Involved in Excision Repair.- IV. Ligation.- V. Heterogeneity of Damage and Repair.- VI. Preferential DNA Repair in Active Genes.- VII. Human Genes for Repair.- VIII. Repair of DNA and Strand Breaks.- C. Repair of Alkylated Bases.- D. Mechanisms of Tolerance.- I. DNA Synthesis on Damaged Templates.- II. Inducible DNA Processing.- E. Mismatch Repair.- F. Concluding Remarks.- References.- 4 Cancer-Prone Human Disorders with Defects in DNA Repair.- A. Introduction.- B. Xeroderma Pigmentosum.- I. Clinical Symptoms.- II. Cellular Sensitivities.- III. DNA Repair.- 1. Excision Repair.- 2. Correction of the Defect.- IV. XP Variants.- V. Mutagenesis.- VI. UV-Inducible Functions.- VII. Relationship to Clinical Symptoms.- C. Cockayne’s Syndrome.- I. Clinical Symptoms.- II. Cellular and Molecular Studies.- III. Relationship to Clinical Symptoms.- D. Trichothiodystrophy.- E. Ataxia-Telangiectasia.- I. Clinical Symptoms.- II. Cellular Sensitivities.- III. DNA Repair.- IV. DNA Synthesis and the Cell Cycle.- V. Cytogenetics.- VI. Mutagenesis.- VII. Growth Properties.- 1. Growth Rate and Lifespan.- 2. Cellular Proteins.- VIII. Relationship to Clinical Symptoms.- F. Fanconi’s Anaemia.- I. Clinical Symptoms.- II. Cellular Sensitivities.- III. Cytogenetics.- IV. DNA Synthesis and the Cell Cycle.- V. DNA Repair.- VI. Other Cellular Aspects.- VII. Mutagenesis.- G. Bloom’s Syndrome.- H. Heterozygotes.- I. Future Prospects: Cloning the Genes.- References.- 5 DNA Repair and Carcinogenesis by Alkylating Agents.- A. Introduction.- B. Alkylating Carcinogens.- I. Classes of Compounds.- II. Spectrum of DNA Adducts.- III. Structure of Adducted DNA and Mutagenesis.- C. Factors Influencing Potency and Specificity of Alkylating Carcinogens.- D. Repair of Alkylated DNA in Mammalian Cells.- I DNA Repair In Vivo.- II. Properties of DNA Repair Proteins.- III. Distribution of Mammalian DNA Repair Activities.- E. Correlation of Adduct Persistence with Tumor Initiation.- I. Single-Dose Experiments.- II. Chronic Dose Experiments.- III. Role of Induction of DNA Repair Processes.- IV. Summary of In Vivo Adduct Persistence Experiments.- F. Cell-Specific DNA Repair.- G. Fine-Structure Specificity in DNA Repair.- I. Repair in Specific Genes and Regions of Chromatin.- II. Sequence Specificity of DNA Alkylation, Repair and Mutagenesis.- H. Correlation of Mutations in Oncogenes with DNA Damage and Repair.- I. Transfer and Expression of DNA Repair Genes.- J. Conclusions.- References.- II. Modifiers of Chemical Carcinogenesis.- 6 Tumour Promotion: Biology and Molecular Mechanisms.- A. Introduction.- B. Tumour Promotion in Mouse Skin.- I. Characteristics of Initiation and Promotion.- II. Models of Tumour Promotion.- 1. Clonal Expansion.- 2. Two-Stage Model for Promotion.- 3. Assessment of One- and Two-Stage Models.- III. Molecular Mechanism of Phorbol Ester-Induced Tumour Promotion.- 1. Specific Binding Sites Mediate Many Phorbol Ester Actions.- 2. Protein Kinase C is a Major Cellular Target for Phorbol Esters.- 3. Are All Phorbol Ester Effects Mediated via Protein Kinase C?.- 4. Do Non-Phorbol Ester Tumour Promoters Activate Protein Kinase C?.- C. Tumour Promotion in Liver.- I. Outline of Chemical Carcinogenesis.- II. Characteristics of Initiated Hepatocytes and Their Progeny.- III. Characteristics of Promotion by Phénobarbital.- IV. Alternative Regimes for Promotion.- V. Mechanism of Promotion by Phénobarbital and Related Xenobiotics.- 1. Mechanisms at the Cellular Level.- 2. Mechanisms at the Molecular Level.- D. Concluding Remarks.- References.- 7 Inhibition of Chemical Carcinogenesis.- A. Introduction.- B. Multistage Carcinogenesis in Mouse Skin.- C. Inhibitors of Tumor Initiation.- I. Antioxidants.- II. Flavones and Polyhydroxylated Compounds.- III. Halogenated Hydrocarbons and Other Enzyme Inducers.- IV. Weakly Carcinogenic or Noncarcinogenic Polycyclic Aromatic Hydrocarbons.- V. Miscellaneous Inhibitors of Tumor Initiation.- D. Inhibition of Tumor Promotion.- I. Antiinflammatory Steroids.- II. Retinoids.- III. Protease Inhibitors.- IV. Inhibitors of Arachidonic Acid Metabolism.- V. Antioxidants.- VI. Polyamine Synthesis Inhibitors.- VII. Miscellaneous Inhibitors of Tumor Promotion.- E. Conclusions.- References.- 8 Genetic Susceptibility to Chemical Carcinogens.- A. Introduction.- B. Genetic Susceptibility to Cancer in Experimental Animals.- I. Inbred Mouse Strains.- II. Interaction Between MHC Type and Chemical Carcinogens.- III. Genetic Interactions with Chemical Carcinogens in Animals.- 1. Lymphoma.- 2. Hepatoma.- 3. Lung.- 4. Mammary Gland.- 5. Other Tumours.- IV. Transplacental Carcinogenesis and Multigeneration Experiments.- C. Genetic Susceptibility to Cancer in Humans.- I. Association of Cancer with Normal Traits.- II. Cancer Families.- 1. Mendelian Inheritance.- 2. Familial Aggregation.- III. Evidence in Humans of Genetic Susceptibility to Chemical Carcinogens.- 1. Second Neoplasms.- 2. Migrant Studies.- 3. Susceptibility to Specific Carcinogenic Agents.- IV. Risk in Families of Patients with Chemically Induced Cancer.- D. Mechanisms of Genetic Susceptibility.- I. Genetic Factors in the Metabolism of the Carcinogen.- 1. Animal Evidence.- 2. Human Evidence of Genetic Control of Aryl Hydrocarbon Hydroxylase.- 3. Genetic Variation in the Cytochrome P-450 System in Humans.- 4. Agents Other Than Polycyclic Aromatic Hydrocarbons.- II. DNA Repair.- III. Genetic Effects on the Environment of the Chemically Transformed Cell.- E. Consequences of Genetic Variation in Chemical Carcinogenesis.- References.- 9 Interactive Effects Between Viruses and Chemical Carcinogens.- A. Introduction.- B. Cervical Cancer.- C. Skin Cancer.- D. Alimentary and Respiratory Tract Cancer.- E. Liver Cancer.- F. In Vitro Studies.- G. Mechanisms of Transformation.- H. Conclusions.- References.- III. Oncogenes in Tumour Development.- 10 Human Oncogenes.- A. Introduction.- B. Identification of Oncogenes.- I. Viral Oncogenes and Proto-Oncogenes.- II. Viral Integration Sites.- III. Transfection Assay.- IV. Translocational Breakpoints.- V. Other Routes.- 1. Structural Homology.- 2. Functional Homology.- 3. Cloning Amplified Sequences.- 4. Transformation by DNA Tumour Viruses.- 5. Recessive Oncogenes.- VI. Conclusions.- C. Activation of Proto-Oncogenes in Human Malignancies.- I. Viruses.- II. Growth Factors and Their Receptors.- 1. EGF Receptor (c-erbB1).- 2. c-erbB2 Receptor.- 3. Other Receptors.- 4. Growth Factors.- III. Protein Kinases.- 1. c-abl.- 2. Others.- IV. Nuclear Proteins.- 1. c-myc.- 2. myc Family.- V. Guanine Nucleotide Binding Proteins.- 1. ras.- 2. Others.- D. Conclusions.- References.- 11 Recessive Oncogenes and Anti-Oncogenes.- A. Introduction.- B. Malignancy in Cell Hybrids.- I. Dominant vs Recessive.- II. Role of Differentiation.- C. Paediatric Cancer Predisposition Syndromes.- I. Retinoblastoma.- II. Wilms’ Tumour.- III. Chromosome Analysis of Tumour Cells.- 1. Retinoblastoma.- 2. Wilms’ Tumour.- IV. Homozygosity Studies.- D. Isolation of Cancer Genes.- I. Retinoblastoma.- II. Prenatal Diagnosis.- III. Wilms’ Tumour.- IV. N-myc Expression.- E. Conclusions.- References.- 12 The Role of Oncogene Activation in Chemical Carcinogenesis.- A. Introduction.- B. Detection of Activated Genes.- I. DNA Transfection.- II. Oligonucleotide Probes.- III. RNA Mismatch.- IV. Restriction Fragment Length Polymorphisms.- C. Oncogene Activation in Chemically Induced Tumours.- I. Skin Papillomas and Carcinomas.- II. Neuroblastomas and Glioblastomas.- III. Mammary Tumours.- IV. Thymomas.- V. Hepatomas.- VI. Fibrosarcomas.- VII. Plasmocytomas.- VIII. Other Animal Models.- D. Oncogene Activation in Cells Transformed in Culture.- I. Rodent Fibroblasts.- II. Mouse Bladder Epithelium.- III. Human Cells.- E. Mechanisms of Oncogene Activation.- I. Evidence of Direct Activation by Chemicals.- II. Evidence for an Indirect Role of Chemical Exposure.- III. Spontaneous Gene Activation.- F. Specificity of Gene Activation.- G. Prospectives.- References.- 13 Growth Factors and Their Receptors.- A. Introduction.- I. Mechanism of Action of Growth Factors.- II. Subversion of the Mitogenic Pathway of Growth Factors in Cell Transformation.- B. Autocrine Growth Factors in Cell Transformation.- I. Platelet-Derived Growth Factor.- II. Transforming Growth Factor ?.- III. Fibroblast Growth Factor and Related Factors.- IV. Bombesin-like Peptides.- V. Interleukins and Colony-Stimulating Factors.- VI. Mechanism of Activation of Growth Factor Expression in Cell Transformation.- C. Perturbations of Growth Factor Receptors in Cell Transformation.- I. Epidermal Growth Factor Receptor.- II. Macrophage Colony-Stimulating Factor Receptor.- III. Receptors with Unknown Ligands (c-neu, c-met, c-ros, c-kit, c-trk, c-ret, c-eph).- IV. Mechanism for Perturbations at the Growth Factor Receptor Level in Cell Transformation.- D. Subversion of Growth Regulatory Pathways in Multistep Carcinogenesis.- References.- 14 Signal Transduction in Proliferating Normal and Transformed Cells.- A. Introduction.- B. Mitogen-Induced Ion Changes.- I. pH Changes.- II. Changes in Ca2+.- III. Phosphorylation.- C. Stimulation of Second Messenger Metabolism.- I. The Inositol Phospholipid Pathways.- 1. G-protein Coupling in the Inositol Lipid Pathway.- 2. Functions of the Second Messengers.- II. cAMP as a Signal for Mitosis?.- III. Interactions Between Signalling Pathways.- D. Involvement of Oncogenes with Signal Transduction.- I. Autocrine Stimulation of Growth.- II. Oncogene Products as Receptors.- III. Effects of Oncogene Products on Signal Transduction Generation.- 1. Gene Products with Tyrosine Kinase Activity.- 2. Involvement of ras Gene Products in Signal Transduction.- E. Conclusions.- References.- 15 Effect of Oncogenes on Cell Differentiation.- A. Introduction.- B. Classification of Oncogenes.- C. Growth Factors and Growth Factor Receptors.- I. Growth Factors.- 1. sis.- 2. Fibroblast Growth Factor-like Oncogenes.- 3. int-1.- 4. Hematopoietic Growth Factors.- II. Growth Factor Receptors.- 1. fins.- 2. erbB.- 3. Other.- D. Tyrosine Kinases.- I. Membrane-Associated Tyrosine Kinase Oncogenes.- 1. Effects on Differentiating Systems.- II. Cytoplasmic Tyrosine Kinases.- 1. fps/fes.- 2. abl.- E. Serine-Threonine Kinases.- I. mos.- II. mil/raf.- F. ras Oncogenes.- G. Nuclear Oncogenes.- I. Factor-Responsive Genes.- 1. myc.- 2. fos.- II. Direct Gene Regulation.- 1. erb A.- 2. jun.- III. Differentiation-Responsive Oncogenes.- 1. myb.- 2. ski.- H. Summary and Perspectives.- I. Cell-Type Specificity of Transformation.- II. Function of Cellular Oncogenes.- III. Stimulation of Cell Growth.- IV. Stimulation of Cell Differentiation.- References.