LEUKOCYTE DNA ADDUCTS AFTER CARCINOGEN EXPOSURE

本申请提出了对循环白细胞的评价， 暴露于致癌物的指标，包括芳胺， 多环芳烃和硝基芳烃， 在职业暴露的情况下。 一只近亲繁殖的老鼠 模型将用于确定DNA的形成- 白细胞中的致癌物是全身的指标 暴露于各类致癌物质。 DNA绑架将 通过32 P-后标记和HPLC分析测量。 剂量反应 急性和亚慢性接触的关系将是 测定 致癌物转移的多样性可通过以下方式确定： 还将探索32 P含量测定和HPLC。 实验将确定是否形成，持久性， 浓度的白细胞DNA绑架后，暴露于 致癌物与靶物质或选定非靶物质相似 致癌物质的组织。 此外，实验 分离培养的小鼠淋巴细胞将决定 这些细胞代谢各种致癌物质， 代谢物。 这项研究的长期目标是开发一种方法， 定量地确定人类职业暴露于 致癌物质，估计癌症的风险程度， 暴露工人，并提供准确的信息，以纠正 措施 第二个目标是探索 通过在体外培养淋巴细胞与致癌物， 可以获得潜在个体风险的一些度量。

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.