Aging, carcinogenesis, and radiation biology the role of nucleic acid addition reactions : [proceedings

The covalent attachment to deoxyribonucleic acid in vivo of a large number of different types of chemical compounds (both normal cellular constituents such as proteins and amino acids, and also exogenous compounds such as drugs, carcinogens, etc. ) have been shown to exert profound effects upon cells. Four research activi­ ties, formerly considered to be totally independent, relate to this problem of nucleic acid adducts--(1) normal covalent attachment of DNA to membranes, protein linkers in chromosomes, etc. ; (2) the roles of radiation and chemical enhancement of DNA adduct formation in cell killing and mutagenesis. (A related field is the use of known cross-linking reactions to gain information on structural associations in macromolecular complexes. ); (3) the relevance of DNA adducts to chemical and radiation carcinogenesis; (4) the rele­ vance of DNA adducts to the cross-linking theory of cellular aging. (1) There are numerous examples of normal linkages between DNA and protein, e. g. , DNA-membrane attachment sites, protein linkers in chromosomes, amino acids covalently linked to DNA as a function of growth conditions, and gene regulation by non-covalently bound proteins. A summary of data on natural adducts to DNA thus serves to introduce the subject of the radiation and chemical enhancement of DNA adduct formation. (2) In the past, radiation biology has been concerned mainly with trying to understand the radiation chemistry of purified DNA, and the biological effects and repair of these radiation-induced alterations when produced in cellular DNA. Front Matter....Pages i-xi Attachment of Chromosomes to Membranes in Bacteria and Animal Cells....Pages 1-10 Linkers in Mammalian Chromosomal DNA....Pages 11-32 Amino Acids Bound to DNA....Pages 33-52 Gene Regulation: Selective Control of DNA Helix Openings....Pages 53-66 Radiation-Induced Cross-Linking of DNA and Protein in Bacteria....Pages 67-81 UV-Induced DNA to Protein Cross-Linking in Mammalian Cells....Pages 83-104 Role of Protein in the Inactivation of Viruses by Ultraviolet Radiation....Pages 105-122 In Vitro Studies of Photochemically Cross-Linked Protein-Nucleic Acid Complexes. Determination of Cross-Linked Regions and Structural Relationships in Specific Complexes....Pages 123-148 Photosensitized Cross-Linking of Proteins to Nucleic Acids....Pages 149-163 Ionizing Radiation-Induced DNA-Protein Cross-Linking....Pages 165-192 Chemically-Induced DNA-Protein Cross-Links....Pages 193-205 Photochemical Addition of Amino Acids and Related Compounds to Nucleic Acid Constituents....Pages 207-223 Addition of Amino Acids and Related Substances to Nucleic Acids by Nucleophilic Catalysis....Pages 225-242 Photochemically-Induced Adducts of DNA....Pages 243-260 Ionizing Radiation-Induced Attachment Reactions of Nucleic Acids and Their Components....Pages 261-286 Repair of DNA Adducts Produced by Alkylation....Pages 287-314 Photoaffinity Labeling of Proteins and More Complex Receptors....Pages 315-340 Chemically and Metabolically Induced DNA Adducts: Relationship to Chemical Carcinogenesis....Pages 341-371 Involvement of Radicals in Chemical Carcinogenesis....Pages 373-398 Role of DNA Repair in Mutation and Cancer Production....Pages 399-442 Cross-Linkage Hypothesis of Aging: DNA Adducts in Chromatin as a Primary Aging Process....Pages 443-492 Dose, Dose Rate, Radiation Quality, and Host Factors for Radiation-Induced Life Shortening....Pages 493-517 Protection of Environmentally Stressed Human Cells in Culture with the Free Radical Scavenger, dl- α -Tocopherol....Pages 519-535 Role of DNA Repair in Aging....Pages 537-556 Back Matter....Pages 557-561