Physical and chemical agents in the environment damage the DNA of humans, and pose a major threat to human health today, and to the genetic integrity of human populations. Although studies on isolated DNA in vitro, on prokaryotes, on mammalian cells in culture, and on laboratory animals have provided essential background information, it is now possible to study DNA damage and repair in human tissues directly. New techniques of high sensitivity, especially those not requiring radioactive labeling have made possible quantitation of DNA damage and repair, as well as detection of residual, unrepaired DNA lesions . In recent years, several investigators have taken up the challenge of studying damage and repair responses in humans, and we have chosen that work as the special focus of this Symposium. Major advances in under­ standing damage and responses in human skin, in blood cells and in human internal organs indicate three major themes. First, DNA damage levels in human tissues depend not only on the initial exposures, but also on the capapacity of that tissue for repair of the specific lesion type. Second, repair in human tissues may differ quantitatively and qualitatively from that in human cells in culture.

Inhalt

DNA Lesion Measurement in Human Tissues.- Measurement of DNA Adducts by Immunoassays.- Detection of Human DNA Adducts by 32P-Postlabeling.- Immunologic Methods for the Detection of Carcinogen Adducts in Humans.- Lesion Measurement in Non-Radioactive DNA by Quantitative Gel Electrophoresis.- Fluorescence Detection of Lesions in DNA.- Damage and Repair in Skin.- Solar Radiation Induced Skin Cancer and DNA Photoproducts in Humans.- Defective DNA Repair in Humans: Clinical and Molecular Studies of Xeroderma Pigmentosum.- 5-MOP Induced Protection Against Epidermal DNA Damage by Ultraviolet Radiation in Human Skin.- Variability in DNA Repair in Human Skin.- Effects of Chemicals on Photobiologic Reactions of Skin.- Repair of 8-MOP Photoadducts in Human Lymphocytes.- Human Skin: Biochemistry and Molecular Biology.- DNA Damage and Repair in Human Skin: Pathways and Questions.- Unscheduled DNA Synthesis in Human Skin.- DNA Repair in Mammalian Tissues and Cells.- Damage Specific Mammalian Endonucleases.- Model Systems for Human Skin.- Characteristics of DNA Excision Repair in Nondividing Xeroderma Pigmentosum Cells, Complementation Group C.- Prospects for Epithelial Gene Therapy.- The Significance of DNA Damage and Repair Mechanisms in Health Risk Assessment.- DNA Damage and Repair in Human Blood Cells.- Measurements of Genomic and Gene-Specific DNA Repair of Alkylation Damage in Cultured Human T-Lymphocytes.- Peripheral Blood Leukocytes as a Surrogate Marker for Cisplatin Drug Resistance: Studies of Adduct Levels and the Repair Gene ERCCl.- Factors Which Affect DNA Repair in Human Lymphocytes.- Methyl Transferase Activity in Secondary Leukemia.- The Single Cell Gel Assay: A Sensitive Technique for Evaluating Intracellular Differences in DNA Damage and Repair.- Detection and Analysis of Human Mutations.- Cytogenetic Investigations of DNA Damage in Aging: A Twin Study.- Studies of DNA Alterations in In Vivo Somatic Cell Mutations in Humans.- Mechanisms of Induction of Specific Chromosomal Alterations.- Unfolding Perspectives on the Genetic Effects of Human Exposures to Radiation.- Effects of Caloric Restriction on the Maintenance of Genetic Fidelity.- Internal Organs.- Oncogenes and Tumor Suppressor Genes Involved in Human Lung Carcinogenesis.- Activation of Carcinogens by Human Liver Cytochromes P-450.- Repair of 06-Methylguanine Damage in Normal Human Tissues.- Repair of 04-Alkylthymine Damage in Human Cells.- Alkylation Repair in Human Tissues.- Participants.