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.

这项生化研究的目标是 1) 严格测试 本实验室发展的构效关系理论 过去20年，2）增加我们对事物本质的理解 参与多核代谢活化的反应 芳香烃，以及 3) 了解造成这一惊人现象的原因 此类化合物的构效关系。 这 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 32P 后标记以及许多方法进行比较 参考化合物及其对亲电子中间体的活化 与核酸反应的物质将在大鼠体内和体外进行研究 肝、肺和皮下组织。 我们期望能够区分 碳氢化合物的致癌反应与致癌反应之间的关系 导致失活的反应。 这些的长期目标 研究目的 1) 正确预测多核物质的致癌性 芳香烃从其结构特征和 代谢，以及 2) 在代谢研究中评估 皮下组织与肺和肝相比，更容易致癌 由多核芳香烃。 更全面的了解 多核反应中最重要的结构特征和反应 芳香烃致癌作用最终可能导致找到治疗方法 预防目前被认为是最重要的一些人类癌症 由此类化学致癌物引起。