BIOALKYLATION IN CHEMICAL CARCINOGENESIS

化学致癌作用中的生物烷基化

• 批准号: 3189116
• 负责人: James W Flesher
• 金额: $ 14.91万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-30 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3189116
• 关键词: DNA; S adenosylmethionine; alkyl group; alkylation; anthracenes; benzanthracenes; benzopyrenes; carbopolycyclic compound; carcinogen testing; carcinosarcoma; chemical carcinogen; chemical carcinogenesis; chemical structure function; chrysenes; cytoplasm; diol; epoxides; gas chromatography; high performance liquid chromatography; hydrolysis; laboratory rat; mass spectrometry; methylation; methyltransferase; nuclear magnetic resonance spectroscopy; oxidation; pyrenes; tissue /cell culture; toxin metabolism

The objectives of this biochemical research are 1) to critically test the structure-activity relationship theory developed in this laboratory over the past 20 years, 2) to increase our understanding of the nature of the reactions that are involved in the metabolic activation of polynuclear aromatic hydrocarbons, and 3) to understand the reasons for the striking structure-activity relationships in this class of compounds. The metabolism of a series of closely related hydrocarbons will be investigated and compared, using HPLC, GC/MS, and 32P postlabelling and a number of reference compounds, and their activation to electrophilic intermediates that react with nucleic acids will be studied, in vitro and in vivo, in rat liver, lung, and subcutaneous tissue. We expect to be able to distinguish between the reactions of the hydrocarbons leading to carcinogenesis and the reactions leading to inactivation. The long term objectives of these studies are 1) to correctly predict the carcinogenicity of a polynuclear aromatic hydrocarbon from a knowledge of its features of structure and metabolism, and 2) to assess, in metabolism studies, the susceptibility of subcutaneous tissue, in comparison with lung and liver, to carcinogenesis by polynuclear aromatic hydrocarbons. A more complete understanding of the most important structural features and reactions involved in polynuclear aromatic hydrocarbon carcinogenesis may eventually lead to methods for the prevention of some of the human cancer that is currently considered to be caused by this class of chemical carcinogens.

这项生物化学研究的目标是：1）严格测试 本实验室开发的结构-活性关系理论， （2）在过去的20年里，我们增加了对自然的理解， 参与多核代谢活化的反应 芳烃，3）了解罢工的原因 这类化合物的结构-活性关系。 的 将研究一系列密切相关的碳氢化合物的代谢 并使用HPLC、GC/MS和32 P后标记以及一些 参比化合物及其活化为亲电中间体 将在体外和体内，在大鼠中研究与核酸反应的 肝脏肺和皮下组织 我们希望能够区分 导致致癌作用的碳氢化合物的反应和 导致失活的反应。 这些长期目标 研究是1）正确预测多核的致癌性， 芳烃的结构特征， 代谢，2）在代谢研究中评估 与肺和肝相比，皮下组织对癌变的影响 多核芳香烃 更完整地理解 最重要的结构特征和反应涉及多核 芳香烃致癌作用可能最终导致用于 预防一些目前被认为是 由这类化学致癌物引起。