Overview

This book originated in numerous Gordon Research Conferences and many other meetings of scientists working in chemistry, biophysics, biochemistry, and biology related to mutagenesis and carcinogenesis. It seemed the appro- priate time to sit back and summarize the results of several decades of research in laboratories in different countries. We are very grateful to the Rockefeller Foundation for inviting us to formulate and begin writing the book at the Center for International Studies in Bellagio, Italy, where we were Resident Scholars. We are fortunate to have had the assistance of so many colleagues around the world who cheerfully sent original data, figures, and preprints and lis- tened patiently to us as we worked out the various conflicting ideas in this fast-moving. field. The names of these scientists are found within the tables, figures, and references. There is one person whose contributions we especially wish to acknowl- edge. Professor Heinz Fraenkel-Conrat was present at the inception of this book and throughout the writing encouraged and criticized in apprOximately equal proportion. Finally, his editing and amalgamation of our two styles gave us great comfort. B.S. D.G.

Full Product Details

Author:   Beatrice Singer ,  D. Grunberger ,  D Grunberger
Publisher:   Plenum Publishing Corporation
Imprint:   Plenum Publishing Corporation
Edition:   1983 ed.
Weight:   0.820kg
ISBN:  

9780306414305

ISBN 10:   0306414309
Pages:   348
Publication Date:   01 November 1983
Audience:   Professional and scholarly ,  Professional & Vocational
Format:   Hardback
Publisher's Status:   Out of Stock Indefinitely
Availability:   Out of stock  

Table of Contents

I Introduction.- II Chemicals as Environmental Mutagens and Carcinogens.- III Intrinsic Properties of Nucleic Acids.- A. Introduction 15.- B. Reactions with Water.- 1. Depurination and Depyrimidination.- 2. Deamination.- 3. Phosphodiester Cleavage.- C. Reversible Equilibrium Reactions.- 1. Tautomerism.- 2. Ionization.- 3. Syn-Anti Rotation.- D. Fidelity in Nucleic Acid Synthesis.- E. Transcription and Replication of Modified Templates.- IV Reactions of Directly Acting Agents with Nucleic Acids.- A. Introduction.- B. Simple Nonalkylating Agents.- 1. Nitrous Acid.- 2. Bisulfite.- 3. Hydroxylamine, Methoxyamine.- 4. Hydrazine.- 5. Formaldehyde.- C. Monofunctional Alkylating Agents.- 1. Introduction.- 2. Alkylation of Nucleosides and Nucleotides.- 3. Alkylation of Synthetic Polynucleotides.- 4. Alkylation of Nucleic Acids in Vitro.- 5. Alkylation of Nucleic Acids in Vivo.- a. General Considerations.- b. Chemical Reactions.- D. Bifunctional Alkylating Agents.- E. Cyclic Alkylating Agents.- 1. Mustards.- 2. Lactones.- 3. Epoxides.- F. Vinyl Halides.- 1. Reaction of Metabolites with Monomers.- 2. Reaction of Chloroacetaldehyde with Polymers.- 3. Reaction of Vinyl Halides in Vivo.- G. Alkyl Carbamates.- V Metabolic Activation of Carcinogens and Mutagens.- A. Enzymatic Activation of Polycyclic Aromatic Hydrocarbons.- 1. Introduction.- 2. Monooxygenases or Arylhydrocarbon Hydrolases.- a. Distribution.- b. Assay of Arylhydrocarbon Hydrolases.- 3. Cytochrome P-450.- a. Mechanism of Induction.- b. Rabbit Microsomal Cytochromes P-450.- c. Rat Microsomal Cytochromes P-450.- d. Mouse Microsomal Cytochromes P-450.- e. Human Liver Microsomal Cytochomes P-450.- 4. NADPH-Cytochrome P-450 Reductase.- 5. Epoxide Hydrolase.- a. Distribution.- b. Assay of Epoxide Hydrolase.- c. Regulation of Epoxide Hydrolase Induction.- d. Mechanism of Epoxide Hydrolase Action.- 6. Conjugation Enzymes.- a. Glutathione-S-Transferase.- b. Sulfotransferase.- c. UDP-Glucuronyl Transferase.- d. Relationship between Conjugation Reactions and Carcinogenicity.- B. Specific Metabolites of Polycyclic Aromatic Hydrocarbons.- 1. Benzo[a]pyrene.- 2. Other Polycyclic Aromatic Hydrocarbons.- a. Benz[a]anthracene.- b. 7-Methlbenz[a]anthracene.- c. 7,12-Dimethylbenz[a]anthracene.- d. 3-Methlycholanthrene.- C. Enzymatic Activation of N-Substituted Aromatic Compounds and Resulting Metabolites.- 1. N-Oxidation to Arylhydroxamic Acids.- 2. N-Oxidation of Arylamines.- 3. Sulfotransferase.- 4. N,O-Acyltransferase.- 5. Deacetylases.- 6. Free Radical Activation.- 7. O-Glucuronides of Arylhydroxamic Acids.- 8. N-Glucuronides of Arylhydroxylamines.- D. Summary.- VI Reactions of Metabolically Activated Carcinogens with Nucleic Aclds.- A. Detection of DNA-Carcinogen Adducts.- 1. Characterization of DNA-Carcinogen Adducts.- 2. Postlabeling Methods to Detect DNA-Carcinogen Adducts.- 3. Radioimmunoassay of DNA-Carcinogen Adducts.- B. Polycyclic Aromatic Hydrocarbons.- 1. Benzo[a]pyrene.- 2. Benz[a]anthracene.- 3. 7-Methylbenz[a]anthracene.- 4. 7,12-Dimethylbenz[a]anthracene.- 5. 3-Methylcholanthrene.- C. N-Substituted Aromatic Compounds.- 1. N-2-Acetylaminofluorene.- 2. N-Methyl-4-Aminoazobenzene.- 3. 2-Naphthylamine.- 4. 1-Naphthylamine.- 5. Benzidine.- 6. 4-Nitroquinoline-1-0xide.- 7. Heterocyclic Amines from Amino Acid and Protein Pyrolysates.- a. Characterization.- b. Metabolic Activation and Binding to DNA.- D. Naturally Occurring Carcinogens.- 1. Aflatoxins.- a. Biological Effects.- b. Metabolism and Activation of AFB1.- c. Formation of DNA Adducts.- 2. Sterigmatocystin.- 3. Safrole.- 4. Estragole.- VII Conformation of DNA Modified by Bulky Aromatic Carcinogens.- A. Introduction.- B. Methods of Analysis.- C. Conformation of DNA-7,8-Dihydrodiol-9,lO-Oxide-Benzo[a]pyrene Adducts.- D. Conformation of DNA Modified by N-Substituted Aromatic Compounds.- 1. Conformation of Acetylaminofluorene- and AminofluoreneModified DNA.- 2. Conformation of DNA Modified by N-Hydroxy-1-Naphthylamine.- VIII Repair in Mammalian Organs and Cells.- A. Introduction.- B. In Vivo Removal of Alkyl Derivatives.- C. Mechanisms of Repair of Alkyl Derivatives in Eukaryotes.- D. In Vivo Removal of Aromatic Derivatives.- IX Site-Directed Mutagenesis.- Appendix A UV Spectral Characteristics and Acidic Dissociation Constants of Modified Bases, Nucleosides, and Nucleotides.- Appendix B Acid, Neutral, and Basic Spectra of Bases, Nucleosides, Nucleotides, and 55 Modified Derivatives.

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