This book is based on the papers presented at the conference on "Mecha nisms of DNA Damage and Repair: Implications for Carcinogenesis and Risk Assessment," held at the National Bureau of Standards on June 2-7, 1985, This volume deals with mechanisms of DNA damage and repair at the molecular level; consequences of unrepaired or misrepaired damage, with major emphasis on carcinogenesis; drugs which bind selectively to altered and potentially damaging DNA sequences; and potential utilization of DNA damage as an endpoint for assessing risks of UV light, ionizing radiations, chemicals, drugs, and hazardous agents in foods. Because the induction of mutations by radiation and genotoxic chemicals has been observed to follow one-hit kinetics in some instances, it is generally assumed that any level of exposure to a DNA-damaging agent may increase the risk of genetic disease or cancer in an exposed population. At the same time, however, there is evidence that although the DNA of living cells is continually damaged by natural background radiation, free radicals, and other naturally occurring processes, most of the damage is normally repaired.
Author(s): Michael G. Simic (auth.), Michael G. Simic, Lawrence Grossman, Arthur C. Upton, David S. Bergtold (eds.)
Series: Basic Life Sciences 189
Edition: 1
Publisher: Springer US
Year: 1986
Language: English
Pages: 578
Tags: Organic Chemistry
Front Matter....Pages i-xv
Introduction to Mechanisms of DNA Damage and Repair....Pages 1-8
History of Radiation Biology from a Personal Point of View....Pages 9-17
Comparison of Mechanisms for DNA Strand Break Formation by the Direct and Indirect effect of Radiation....Pages 19-27
Electron Spin Resonance Studies of the Mechanism of Radiation Damage to DNA....Pages 29-37
Free Radical Mechanisms of DNA Base Damage....Pages 39-49
Peroxyl Radicals of Nucleic Acids and their Components....Pages 51-59
Radiation-Induced Peroxidation of DNA and Effects of Redox-Active Agents....Pages 61-67
The Radiation Chemistry of the Purine Bases within DNA and Related Model Compounds....Pages 69-74
Bacteriophage DNA as a Model for Correlation of Radical Damage to DNA and Biological Effects....Pages 75-87
Ultrafast Chemical Repair of DNA Single and Double Strand Break Precursors in Irradiated V79 Cells....Pages 89-100
Assessment of DNA Damage by Filter Elution Assays....Pages 101-118
DNA Modification by Sulfur Mustards and Nitrosoureas and Repair of these Lesions....Pages 119-125
Intragenomic Localization of Carcinogen-DNA Damage....Pages 127-134
Ionizing Radiation Induced DNA Damage: Identities and DNA Repair....Pages 135-138
Effects of LET ∞ on the Fate of DNA Damage Induced in Rabbit Sensory Cells In Situ : Fundamental Aspects....Pages 139-150
Radiation Damage to DNA in Various Animal Tissues: A Comparison of Yields and Repair In Vivo and In Vitro ....Pages 151-158
Differential Regulation of Base and Nucleotide Excision Repair in Mammalian Cells....Pages 159-170
Immediate and Repair Induced DNA Double Strand Breaks in Mammalian Cells....Pages 171-180
DNA-Protein Cross-Links: New Insights into their Formation and Repair in Irradiated Mammalian Cells....Pages 181-192
DNA-to-Protein Crosslinks and Backbone Breaks caused by Far- and Near-Ultraviolet, and Visible Light Radiations in Mammalian Cells....Pages 193-202
Sequence Specificity and Biological Consequences of Drugs that Bind Covalently in the Minor Groove of DNA....Pages 203-210
Molecular Recognition of DNA Binding Agents: High-Field 1 H and 3 1 P One- and Two-Dimensional NMR Studies on the 1:1 Intercalation Complexes of Mitoxantrone with Selected Oligodeoxyribonucleotides....Pages 211-218
DNA Binding and Biological Properties of Bis and Tris Interacting Molecules....Pages 219-230
Novel Types of DNA-Sugar Damage in Neocarzinostatin Cytotoxicity and Mutagenesis....Pages 231-244
DNA-Drug Binding and Control of Genetic Information....Pages 245-255
Computer-Aided Design of New DNA Intercalators....Pages 257-264
Differential Expression of SOS Genes in an E. Coli Mutant Producing Unstable LexA Protein Enhances Excision Repair But Inhibits Mutagenesis....Pages 265-271
Mutagenic DNA Repair in Bacteria: The Role of UmuDC and MucAB....Pages 273-280
The Repair of Pyrimidine Dimers Via a DNA-Glycosylase Mechanism....Pages 281-286
The Involvement of an E. Coli Multiprotein Complex in the Complete Repair of UV-Damaged DNA....Pages 287-294
Pyrimidine Dimers Induced Alteration of DNA Tertiary Structure Evidence for Unwinding and Shortening....Pages 295-301
Mismatch Correction....Pages 303-310
Molecular Approaches to the Study of Nucleotide Excision Repair in Eukaryotes....Pages 311-318
Restoration of DNA Repair in UV-Sensitive Chinese Hamster Ovary Cell by the denV Gene from Bacteriophage T4....Pages 319-326
The Adaptive Response of Mammalian Cells to Alkylating Agents....Pages 327-334
DNA Glycosylases in DNA Repair....Pages 335-340
Apurinic Sites as Common Intermediates in Mutagenesis....Pages 341-347
The Repair of Uracil-Containing DNA....Pages 349-356
Metabolic Consequences of DNA Damage: The Role of Poly (ADP-Ribose) Polymerase as Mediator of the Suicide Response....Pages 357-363
DNA Damage, DNA Repair and Induced Mutagenesis: Some Enzymological and Structural Considerations....Pages 365-375
Mechanisms of Mutagenesis of E. Coli by Ultraviolet Light....Pages 377-383
Activation of H- ras -1 Oncogenes by Chemical Carcinogens....Pages 385-397
Activation of the c- myc Oncogene....Pages 399-406
Salmonella Tester Strains: Mutational Targets and Correlation with Animal Carcinogenicity and Teratogenicity....Pages 407-424
Mechanisms of Spontaneous Mutagenesis: Clues from Mutational Specificity....Pages 425-437
Use of Gradient Denaturing Gels to Determine Mutational Spectrum in Human Cells....Pages 439-452
Urinary N-Nitrosamino Acids as Indices of Endogenous Formation of N-Nitroso Compounds....Pages 453-461
Application of Monoclonal Antibodies to Monitor Human Exposure to Aflatoxin B1....Pages 463-471
Blood Proteins as Carcinogen Dosimeters....Pages 473-478
Development of an Avidin-Biotin Amplified Enzyme-Linked Immunoassay for Detection of DNA Adducts of the Human Bladder Carcinogen 4-Aminobiphenyl....Pages 479-488
Intragenomic Heterogeneity in DNA Damage Processing: Potential Implications for Risk Assessment....Pages 489-498
The Role of Pharmacokinetics in Risk Assessment....Pages 499-507
Immunologic Quantification of Carcinogen-DNA Adducts....Pages 509-517
Interpretation of Genotoxicity Data in Assessing the Risks of Genetic Diseases....Pages 519-527
Background Levels of DNA Damage in the Population....Pages 529-535
Use of Models in Low-Dose Extrapolation....Pages 537-542
Problems in Interspecies Comparisons....Pages 543-549
The Time to Tumor Approach in Risk Assessment....Pages 551-556
The Role of Nutritional Factors in Cellular Protection Against DNA Damage, Altered Gene Expression and Malignant Transformation....Pages 557-562
The Role of Risk Assessment in Food Safety Policy....Pages 563-571
Back Matter....Pages 573-578
