Organ and Species Specificity in Chemical Carcinogenesis

The Symposium on Organ and Species Specificity in Chemical Carcinogenesis was held March 1981 in Raleigh, North Carolina. Dr. James Miller concluded this Symposium with these remarks: "Without a doubt all of us would agree this has been a very successful symposium in illustrating a very wide range of chemical, stereochemical, biochemical, metabolic, molecular, and biological factors in chemical carcinogenesis. I think it is noteworthy that many of the discussions have dealt with pharmacodynamic, or toxicodynamic, factors that can influence the biological activities of the extremely wide range of structures that we choose to call chemical carcinogens. I sincerely hope that after this symposium everyone here will realize the very great need we have for further information on these agents in the species we profess to be working for, the human species. We badly need an adequate data base on human organs, human tissues, human cells, human subcellular preparations, and human body fluids. I don't think we can rely on extrapolations of data on chemical carcinogenesis from experimental animals to humans, no matter how sophisticated or plausible these extrapolations may seem, until we know far more about chemical carcinogenesis in humans. Now, I'd like to add a somewhat personal note. As many of you know, my wife and I have shared a joint career of some 40 years in this field, and I'd like to emphasize in these closing remarks the factor of youth. Front Matter....Pages i-ix The Nature of Organ Specificity in Chemical Carcinogenesis....Pages 1-22 Species Differences in Response to Aromatic Amines....Pages 23-47 Aflatoxin B 1 : Correlations of Patterns of Metabolism and DNA Modification with Biological Effects....Pages 49-62 Species Specificity in Nitrosamine Carcinogenesis....Pages 63-75 Organ Specificity and Interspecies Differences in Carcinogenesis by Metabolism-Independent Alkylating Agents....Pages 77-105 Organ and Species Specificity in Nickel Subsulfide Carcinogenesis....Pages 107-127 Chemical Carcinogenesis Studies in Nonhuman Primates....Pages 129-156 Organ Specificity and Tumor Promotion....Pages 157-171 Skin Tumor Promotion: A Comparative Study of Several Stocks and Strains of Mice....Pages 173-188 The Role of Phorbol Ester Receptor Binding in Responses to Promoters by Mouse and Human Cells....Pages 189-200 Tissue and Species Specificity for Phorbol Ester Receptors....Pages 201-229 Liver as a Model System for Analyzing Mechanisms of Tumor Initiation and Promotion....Pages 231-252 Promotion of Urinary Bladder Carcinogenesis....Pages 253-272 Species and Organ Differences in the Biotransformation of Chemical Carcinogens....Pages 273-281 Species Heterogeneity in the Metabolic Processing of Benzo[a]pyrene....Pages 283-294 Endocrine Regulation of Xenobiotic Conjugation Enzymes....Pages 295-312 Multiple Effects and Metabolism of α-Naphthoflavone in Induced and Uninduced Hepatic Microsomes....Pages 313-329 Species Differences in the Activation of Benzo[a]pyrene in the Tracheal Epithelium of Rats and Hamsters....Pages 331-351 Subcellular Metabolic Activation Systems: Their Utility and Limitations in Predicting Organ and Species Specific Carcinogenesis of Chemicals....Pages 353-375 Cell-Mediated Mutagenesis, an Approach to Studying Organ Specificity of Chemical Carcinogens....Pages 377-390 The Activation of Carcinogens by Mammary Cells: Inter-Organ and Intra-Organ Specificity....Pages 391-404 Studies on the Mode of Action of Chemical Carcinogens in Cultured Mammalian Cells....Pages 405-427 Comparison of the Sensitivity of Rodent and Human Cells to Chemical Carcinogens Using Viral Transformation, DNA Damage, and Cytotoxicity Assays....Pages 429-449 Tissue-Specific Sister Chromatid Exchange Analyses in Mutagen-Carcinogen Exposed Animals....Pages 451-472 Metabolism of Chemical Carcinogens by Tracheobronchial Tissues....Pages 473-495 Introduction: DNA Damage and Repair....Pages 497-508 DNA Modification and Repair in Vivo : Towards a Biochemical Basis of Organ-Specific Carcinogenesis by Methylating Agents....Pages 509-529 Modification of DNA Repair Processes Induced by Nitrosamines....Pages 531-543 Repair of Alkylated DNA by Cell Extracts from Various Organs and Species....Pages 545-563 Time-Dependent Differences in the Benzo[ a ]pyrene-DNA Adducts Present in Cell Cultures from Different Species....Pages 565-586 DNA Binding as a Probe for Metabolic Activation in Various Systems....Pages 587-604 Cell Specificity in DNA Damage and Repair....Pages 605-617 DNA Adduct Formation and Removal in N-Acetoxy-2-Acetylaminofluorene-Exposed Cultured Cells and in Organs from Rats Fed 2-Acetylaminofluorene....Pages 619-635 Trans-Species and Trans-Tissue Extrapolation of Carcinogenicity Assays....Pages 637-651 Carcinogenic Risk Assessment—The Consequences of Believing Models....Pages 653-665 Back Matter....Pages 667-693