MONOCLONAL ANTIBODIES SPECIFIC FOR CYCLIC DNA ADDUCTS

人类暴露于多种致癌物和潜在致癌物中 包括丙烯醛，巴豆醛，N-亚硝基吡咯烷，环磷酰胺， 乙二醛，甲基乙二醛，N-亚硝基吗啉，N-亚硝基二乙醇胺， 米索硝唑、氯乙烯、氯乙醛和氨基甲酸乙酯。 这些 化合物存在于环境、食物链和职业中， 医疗环境。 暴露于这些化合物可导致 DNA和/或RNA中的环状核苷加合物。 目前的分析方法 不足以检测暴露于以下物质的人的组织中的这些加合物： 这些化合物。 最近，已经开发了灵敏的免疫测定法， 检测到大量的DNA加合物。 这些测定中的一些已经被 用于筛查暴露于环境致癌物的人类。 在这 项目我们打算开发单克隆抗体特异性6环 由上述化合物形成的核苷加合物。 这些单克隆抗体将用于开发敏感的 免疫印迹法检测这些加合物的DNA从 动物的组织，最终是人类，暴露在这些化合物中。 的 这些试验对人体研究的适用性将通过以下方式证明： F344染毒大鼠外周血和肝脏DNA含量测定 这些化合物。 这些实验将确定暴露水平 这些化合物是形成可检测水平的DNA所必需的 加合并建立外周血白色DNA的有效性 细胞作为暴露于这些化合物的指标。 的发展 这些高灵敏度的免疫测定代表了一种有价值的方法， 1)了解加合物形成的机制及其在肿瘤中的作用 2）监测和控制此类风险， 其有害影响。

Humans are exposed to a variety of carcinogens and potential carcinogens including acrolein, crotonaldehyde, N-nitrosopyrrolidine, cyclophosphamide, glyoxal, methylglyoxal, N-nitrosomorpholine, N-nitrosodiethanolamine, misonidazole, vinyl chloride, chloracetaldehyde and ethyl carbamate. These compounds are present in the environment, food chain and occupational or medical settings. Exposure to these compounds can lead to the formation of cyclic nucleoside adducts in DNA and or RNA. Current analytical methods are inadequate to detect these adducts in tissues of persons exposed to these compounds. Recently, sensitive immunoassays have been developed for the detection of a number of DNA adducts. Some of these assays have been used to screen humans exposed to environmental carcinogenes. In this project we intend to develop monoclonal antibodies specific for 6 cyclic nucleoside adducts which are formed by the above mentioned compounds. These monoclonal antibodies will be used in the development of sensitive immunoblotting assays for the detection of these adducts in DNA from tissues of animals, and eventually humans, exposed to these compounds. The applicability of these assays to human studies will be demonstrated by assaying DNA isolated from peripheral blood and liver of F344 rats exposed to these compounds. These experiments will establish the level of exposure to these compounds necessary for the formation of detectable levels of DNA adduct and establish the validity of using DNA from peripheral blood white cells as an indicator of exposure to these compounds. The development of these highly sensitive immunoassays represents a valuable approach toward 1) understanding the mechanisms of adduct formation and their role in tumor formation and 2) monitoring and controlling such exposures and preventing their deleterious effects.