MONOCLONAL ANTIBODIES SPECIFIC FOR CYCLIC DNA ADDUCTS

人类接触到多种致癌物质和潜在致癌物质 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、 咪唑、氯乙烯、氯乙醛和氨基甲酸乙酯。这些 化合物存在于环境、食物链和职业或 医疗环境。暴露在这些化合物中会导致 DNA和或RNA中的环状核苷加合物。当前的分析方法 不足以在接触过的人的组织中检测到这些加合物 这些化合物。最近，灵敏的免疫分析方法已经被开发出来用于 一些DNA加合物的检测。其中一些检测已经被 用于筛查接触环境致癌物质的人。在这 我们计划开发针对6个周期的单抗 由上述化合物形成的核苷加合物。 这些单抗将被用于开发敏感的 免疫印迹法检测猪瘟病毒DNA中的这些加合物 动物的组织，最终是人类，暴露在这些化合物中。这个 这些化验方法在人体研究中的适用性将通过以下几个方面得到证明 F344染毒大鼠外周血和肝脏DNA检测 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到的DNA水平所必需的 推断和确定使用外周血白细胞DNA的有效性 细胞作为暴露在这些化合物中的指示器。的发展。 这些高度敏感的免疫分析是一种有价值的方法 1)了解加合物的形成机制及其在肿瘤中的作用 形成和2)监测和控制这种接触并预防 它们的有害影响。

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.