LEUKOCYTE DNA ADDUCTS AFTER CARCINOGEN EXPOSURE

本应用建议评价循环白细胞作为

This application proposes evaluation of circulating leukocytes as indicators of exposure to carcinogens including arylamines, polycyclic aromatic hydrocarbons, and nitroarenes that are encountered in occupational exposure situations. An inbred mouse model will be used to determine if the formation of DNA- carcinogen abducts in leukocytes is an indictor of whole body exposure to the various classes of carcinogens. DNA abducts will be measured by 32P-postlabeling and HPLC analysis. Dose-response relationships for acute and sub-chronic exposures will be determined. The diversity of carcinogen abducts determinable by 32P-assay and HPLC will also be explored. Experiments will determine if formation, persistence, and concentration of leukocyte DNA abducts following exposure to a carcinogen are similar to that of target or selected non-target tissues of the carcinogen. Additionally, experiments with isolated, cultured mouse lymphocytes will determine the ability of these cells to metabolize various carcinogens to DNA active metabolites. The long-range objective of this research is to develop a method of determining, quantitatively, human occupational exposure to carcinogens, estimating the degree of risk of cancer of the exposed worker, and supplying accurate information for corrective measures. A secondary objective is exploring the possibility that through in vitro incubation of lymphocytes with carcinogens, some measure of potential, individual risk can be obtained.