RT Report T1 Methods to Assess DNA Damage and Repair: Interspecies Comparisons A1 Scientific Group on Methodologies for the Safety Evaluation of Chemicals, A2 Beland, Frederick A2 Poirier, Miriam A2 Hoeijmakers, Jan A2 Lehmann, Alan A2 Mulder, G. A2 Natarajan, A. A2 Tucker, J. A2 Sasaki, M. A2 Albertini, R. A2 Nicklas, J. A2 Rebison, S. A2 O'Neill, J. A2 Mullenders, Leon A2 Smith, Charles A2 Vrieling, H. A2 van Zeeland, A. A2 Wood, Michael A2 Verghis, Susan A2 Essigmann, John A2 Waters, Michael A2 Richard, Ann A2 Rabinowitz, James A2 Stack, H. Frank A2 Garrett, Neil A2 Lohman, Paul A2 Rosenkranz, Herbert A2 Ashby, J. K1 biosphere K1 nature conservation K1 carcinogen K1 genetic resource K1 molecular biology K1 mutation K1 risk assessment K1 toxicology K1 toxic substance K1 DNA K1 Health PB John Wiley and Sons Ltd. SN 0-471-94256-1 YR 1994 FD 1994 LK https://wedocs.unep.org/handle/20.500.11822/29685 UL https://wedocs.unep.org/handle/20.500.11822/29685 NO This book evaluates current knowledge of the mechanisms of activation/detoxication of DNA damaging agents, organotropic and cell-structure effects, induction and repair of DNA damage, and the molecular and phenotypical analysis of mutation induction This evaluation is presented in seven contributed papers and a joint report which was prepared at a workshop held at the National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina, USA in March 1990. The joint report includes general recommendations aimed at improving research in this field and developing methodologies for genotoxicity testing, taking account of the potentials and limitations of available animal models. NO ForewordPrefaceAcknowledgementsScientific Group on Methodologies for the Safety Evaluation of ChemicalsParticipants of the WorkshopPart 1 — Joint ReportIntroduction, General Conclusions, and Recommendations1.1 Introduction1.2 Carcinogenesis as a MultiStep Process1.3 Reaction Kinetics and Adduct Monitoring1.4 General Recommendations1.5 ReferencesDNA Damage2.1 Molecular Dosimetry2.1.1 Absorption and Distribution2.1.2 Bioactivation and Detoxification2.1.3 Methods for Molecular Dosimetry2.1.4 Examples of Carcinogen Dosimetry in Humans2.2 Cross-Species Sensitivity in Carcinogenic Response2.3 Approaches to Predict Cancer Activity and Potency2.3.1 Structure–Activity Relationships2.3.1.1 Fragmentation of the Chemistry2.3.1.2 Fragmentation of Biological Parameters2.4 Genotoxicity Profiles in EukaryotesDNA Repair and Mutagenesis3.1 State of Knowledge3.2 Impacts of Preferential Repair3.3 Mechanisms of MutagenesisDNA Repair, Mutagenesis, and Risk Assessment4.1 Introduction4.2 Monitoring of Human PopulationsPart 2 — Contributed ChaptersDNA Adducts and Their Consequences5.1 Introduction5.2 N-Nitrosamines5.3 Aflatoxins5.4 Aromatic Amines5.5 Polycyclic Aromatic Hydrocarbons5.6 Summary5.7 ReferencesNucleotide Excision-Repair Among Species6.1 Introduction6.2 Excision-Repair in Escherichia coli6.3 Excision-Repair in Saccharomyces cerevisiae6.4 Drosophila6.5 Mammalian Cells6.6 Relationship Between Repair Systems of Different Organisms6.6.1 Prokaryotes and Eukaryotes6.6.2 Yeast and Humans6.7 ReferencesInterspecies Determinants: Bioactivation and Inactivation of Carcinogens7.1 Introduction7.2 Exposure and Pharmacokinetic Scaling7.3 Activation of Carcinogens7.4 Prediction of Metabolite Pattern7.5 Protective Systems7.6 Extrapolation from Laboratory Animals to Humans7.7 ReferencesMonitoring Cytogenetic Damage In Vivo8.1 Introduction8.2 Chromosomal Aberrations8.3 Sister Chromatid Exchanges8.4 Micronuclei8.5 Sperm Cytogenetics8.6 Interspecies Comparisons8.7 Conclusions8.8 ReferencesIn Vivo Somatic Cell Gene Mutations in Humans9.1 Introduction9.2 Current Assays for Human In Vivo Somatic Cell Mutations9.3 Other Measures of In Vivo Somatic Cell Gene Mutation9.4 Conclusions9.5 ReferencesDNA Repair in Specific Sequences and Genomic Regions10.1 Introduction10.2 Repair of UV-Induced Lesions10.3 Alterable Repair of UV Damage in Mammalian Genes10.4 Repair of Other Types of Damage10.5 Conclusions10.6 ReferencesMolecular Analysis of Mutations in Endogenous Genes11.1 Introduction11.2 Factors Influencing Mutation Spectra11.3 Target Genes for Analysis of Mutation Spectra11.4 Conclusions11.5 ReferencesMolecular Analysis of Mutations in Shuttle Vectors and Transgenic Animals12.1 Introduction12.2 Operational Features of Shuttle Vector and Transgenic Animal Assays for Mutagenesis12.3 Mutational Specificity of Ultraviolet Light12.4 Mutational Specificity of DNA Alkylating Agents12.5 Mutational Specificity of Aromatic Amines, Amides, and Nitro Compounds12.6 Mutational Specificity of Polycyclic Aromatic Hydrocarbons12.7 Mutational Specificity of Other DNA Damaging Agents12.8 Conclusions12.9 ReferencesStructure-Activity Relationships (SAR): Computerized Systems13.1 Introduction13.2 SAR as a Process13.3 Correlative and Mechanistic Approaches13.4 Correlative SAR Techniques13.5 Genetic Toxicology Databases: The Gene-Tox and NTP Databases13.6 Integration of Structural Concepts with Database Evaluation13.7 SAR Estimations13.8 Weight-of-Evidence Scoring System13.9 Summary and Discussion13.10 ReferencesStructure-Activity Relationships: Experimental Approaches14.1 Introduction14.2 Early Approaches14.3 Criteria and Methods for Interspecies Comparisons14.4 Molecular Genetic Spectra of Procarcinogens14.5 SAR Among Carcinogens/Mutagens in General14.6 Conclusions and Perspectives14.7 ReferencesIndex DS UN Environment Document Repository RD Sep 22, 2026