Mechanisms of Chemical Carcinogenesis

Mechanisms of Chemical Carcinogenesis provides information pertinent to the fundamental mechanisms of chemical carcinogenesis. This book surveys the interactions of chemical carcinogens with native DNA, the activation of normal cellular sequences, and the transforming role of the activated genes. Organized into seven chapters, this book begins with an overview of the relationship between the incidence of lung cancer and the frequency and duration of cigarette smoking. This text then examines the concept that carcinogens may require metabolic activation before they initiate carcinogenesis. Other chapters consider the structure of the nucleoside adducts resulting from the hydrolysis of salmon-sperm DNA and rat-liver ribosomal RNA. This book discusses as well the persistence of nucleoside analogues in target-tissue nucleic acid. The final chapter deals with mutational theory. This book is a valuable resource for workers involved with cancer research, toxicology, and molecular biology. Specialists in drug development, industrial hygiene and occupational medicine will also find this book useful.

1 Introduction Landmarks in the Recognition of Chemical Carcinogenesis Developing Theory from Its Roots in Experiment Bibliography and References2 Activation of Chemical Carcinogens in the Mammal Presumptive Evidence of Metabolic Activation Reactive Metabolites of Chemical Carcinogens Biosynthesis of Reactive Metabolites and Matching Tissue Specificities Bibliography and References3 Authenticated Interactions with Nucleic Acid Aromatic Amines and Amino-Azo Dyes Nitrosamines and 3-Alkyl-1-Phenyltriazines Metals Vinyl Chloride Glycidaldehyde Aflatoxins Polycyclic Aromatic Hydrocarbons Safrole Concluding Remarks Bibliography and References4 Mechanisms in Perspective: Biological Significance of Modified Deoxyribonucleoside Residues in DNA Repair of Biochemical Lesions in DNA Miscoding Induced by Carcinogens during Directed Nucleic Acid Biosynthesis Effects On the Biosynthesis of Inter-Related Macromolecules Bibliography and References5 Mechanisms in Perspective: Inhibition of Tumor Induction Inhibition of Tumor Initiation by Metabolic Inducers and Inhibitors Inhibition of Tumor Initiation by the Interaction of Nucleophiles with Reactive Carcinogen Intermediates Inhibition of Tumor Initiation through the Induction of DNA-Repair Mechanisms Bibliography and References6 Mechanisms in Perspective: Tumor Promotion Two-Stage Carcinogenesis in the Skin System The Croton Oil Promoters Tumor Promoters for Other Physiological Systems Other Experimental Models of Two-Stage Carcinogenesis Mode of Action of Tumor Promotion in the Skin Bibliography and References7 Standard Mutational Theory of Cancer and the Impact of Contingent Advances in Genetics Somatic Cell Mutation Cancer Models The 'Oncogene'/Proto-Oncogene Concept The Developing 'Oncogene' Story Activation of Oncogenes' Proteins Encoded by Activated 'Oncogenes' Concluding Remarks Bibliography and ReferencesIndex