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 References

2 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 References

3 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 References

4 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 References

5 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 References

6 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 References

7 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 References

Index