DNA ADDUCTS AS MOLECULAR DOSIMETERS OF GENOTOXINS

接触遗传毒性物质可由多种职业性和 环境来源。这些试剂的酶激活会导致 亲电体的形成，这些亲电体随后可以反应形成DNA 加合物。DNA加合物的形成被认为起着重要的作用 在人类癌基因激活和癌症发生中的作用。在……里面 这些研究我们将研究苯的活化形成DNA损伤。 这项建议的具体目的是调查； 1.DNA加合物和8-氧脱氧鸟苷的形成和修复 卡介苗对B6C3F1小鼠骨髓和外周血白细胞的影响 苯本身或与其他试剂结合使用。 2.小鼠骨髓髓系部分DNA损伤的形成 B6C3F1小鼠，并与Projects 4和5血祖细胞合作 细胞和外周血液培养将在体外用苯处理 代谢物。 3.在Project 9中，DNA加合物之间的剂量反应关系 水生生物的形成、繁殖和发育反应 有机体。， 4.骨髓ob Big Blue B6C3F1中LacI突变的形成 用苯处理的小鼠。 5.结合项目3，优化结构的程序 ~(32)P-后标记和~(32)P标记鉴定DNA加合物 苯形成的DNA加合物的结构鉴定 代谢物。 这些研究将提供对DNA应用的更好的理解 作为暴露于遗传毒性的分子剂量计的加合测量 探员们。

Exposure to genotoxic agents can occur from av variety of occupational and environmental sources. Enzymatic activation of these agents results in the formation of electrophiles which can subsequently react to form DNA adducts. The formation of DNA adducts is believed to play an important role in the activation of human oncogenes and the initiation of cancer. In these studies we will study the activation of benzene to form DNA damage. The specific aims of this proposal are to investigate; 1. the formation and repair of DNA adducts, and 8-oxodeoxyguanosine in bone marrow and peripheral blood leukocytes of B6C3F1 mice treated with benzene by itself or in combination with other agents. 2. the formation of DNA damage in myeloid fractions of bone marrow of B6C3F1 mice and in collaboration with Projects 4 and 5 blood progenitor cells and peripheral blood cultures will be treated in vitro with benzene metabolites. 3. with Project 9, the dose response relationships between DNA adduct formation and reproductive, and developmental responses in aquatic organisms., 4. the formation of lacI mutations in the bone marrow ob Big Blue B6C3F1 mice treated with benzene. 5. with project 3, to optimize the procedures for structural identification of DNA adducts detected by 32P-postlabeling and identification of the structures of the DNA adducts formed by the benzene metabolites. These studies will provide a better understanding of the application of DNA adduct measurements as a molecular dosimeter for exposure to genotoxic agents.