Individual Susceptibility to Genotoxic Agents in the Human Population

ISBN-13: 9781461297093 / Angielski / Miękka / 2012 / 518 str.

Frederick J. De Serres; Ronald W. Pero;William Sheridan

Opis

As a result of the industrial revolution, man's technological achievements have been truly great, increasing the quality of life to almost unimagined proportions; but all this progress has not been accomplished without equally un imagined health risks. Sufficiently diagnostic short-term assay procedures have been developed in recent years for us to determine that there are mutagenic agents among thou sands of chemicals to which the human population is exposed today. These chemicals were not significantly present prior to the indus trial revolution. As of today, there are no procedures available which have been adequately demonstrated to assess individual sus ceptibility to genotoxic exposures, and as a result we have had to rely on extrapolating toxicological data from animal model systems. The question is can we afford to allow such an increased environ mental selection pressure via mutagenic exposures to occur without expecting adverse long-term effects on our health. It is apparent from this line of reasoning that what is lacking and immediately needed are test procedures that can be applied to humans to assess genotoxic exposure as well as individual susceptibility to it. There have already been two conferences which have focused at tention on this research area. "Guidelines for studies of human populations exposed to mutagenic and reproductive hazards" (A. D. Bloom, ed., March of Dimes Birth Defects Foundation, White Plains, New York, 1981) and "Indicators of genotoxic exposure in humans" (Banbury Report 13, B. A. Bridges, B. E. Butterworth, and I. B."

Spis treści

Session I: Genotoxic Substances and Variability in Human Disease.- Investigation of Genetic Hazards: Guidance from Occupational and Environmental Studies.- Epidemiology and Population Monitoring in Genetic Risk Assessment.- An Overview of Approaches for Genetic Monitoring of Humans.- Evaluation of Genotoxic Effects in Human Populations.- Session II: Metabolism of Genotoxic Agents in Human Cells and its Relevance to Risk Assesment.- On the Possible Significance of TCDD Receptor Based Assays in Attempts to Estimate Environmental Health Hazards.- Interindividual Differences in Monooxygenase Activities of Human Liver.- Involvement of Prostaglandin Synthetase in the Metabolic Activation of Chemical Carcinogens — Phenacetin as an Example.- The Use of Immunological and Molecular Biological Techniques in the Assessment of Occupational and Environmental Disease.- Interindividual Variation in the DNA Binding of Chemical Genotoxins Following Metabolism by Human Bladder and Bronchus Explants.- Session III: Genotoxic Testing on Somatic Cells in the Human Population.- Intrinsic Factors that Can Affect Sensitivity to Chromosome Aberration Induction.- Individual Variability in the Frequency of Sister Chromatid Exchange in Human Lymphocytes.- Variations in Mitotic Index and Chromosomal Aberration Rates in Women.- Micronuclei in Cultured Lymphocytes as an Indicator of Genotoxic Exposure.- Detection of Mutated Erythrocytes in Man.- Peripheral Blood Lymphocytes as Indicator Cells for in vivo Mutation in Man.- Discrimination between Spontaneous and Induced Mutations in Human Cell Populations by Use of Mutational Spectra.- Session IV: Evaluation of Body Tissues and Fluids as Indicators of Exposure.- Short Term Tests on Body Fluids.- Chemical Analysis of Human Samples: Identification and Quantification of Polychlorinated Dioxins and Dibenzofurans.- Hemoglobin as a Dose Monitor of Alkylating Agents: Determination of Alkylation Products of N-Terminal Valine.- Session V: Population Heterogeneity as a Modifier of Genotoxic response.- Variations in Sensitivity and DNA Repair in Human Cells Exposed to Genotoxic Agents.- Unscheduled DNA Synthesis Induced by N-Acetoxy-2-acetylaminofluorene as an Indicator of Risk from Genotoxic Exposures.- Individual Variation in DNA Repair in Human Peripheral Blood Monocytes.- Influence of Demographic Factors on Unscheduled DNA Synthesis as Measured in Human Peripheral Leukocytes and Fibroblasts.- Individual Variation in Benzo(a)pyrene Metabolism and Its Role in Human Cancer.- C-Band Variation in Hypertensive Men.- Session VI: Reproductive Effects of Genotoxic Exposures on the Human Population.- Methods for Evaluating the Effects of Environmental Chemicals on Human Spermatogenesis.- New Techniques for Detecting Chromosome Abnormalities in the Germ-Line in Man.- Epidemiologic Considerations in Assessing Adverse Reproductive Outcomes Following Genotoxic Exposures.- Session VII: Genotoxic Risk Monitoring of the General Population.- A Reference Population: For the Evaluation of Natural Occurring Inter-individual Variation in the Response to Genotoxic Agents.- Investigations of Smoking and Related Health Complications and Genotoxic Hazards in a Preventive Medical Population Program in Malmö, Sweden.