BIOALKYLATION IN CHEMICAL CARCINOGENESIS

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超过了 在过去的20年里，2)增加了我们对经济衰退本质的认识 参与多核代谢激活的反应 芳香烃，以及3)了解罢工的原因 这类化合物的构效关系。这个 将研究一系列密切相关碳氢化合物的新陈代谢。 并利用高效液相色谱、气相色谱/质谱仪和~(32)P后标记法等方法进行了比较 参比化合物及其对亲电中间体的活化作用 将在体外和体内研究与核酸发生反应的大鼠 肝、肺和皮下组织。我们希望能够分辨出 在导致致癌的碳氢化合物的反应和 导致失活的反应。这些项目的长期目标是 研究是：1)正确预测多核物质的致癌性 对芳香烃的结构和结构特征的认识 代谢，以及2)在新陈代谢研究中评估 皮下组织与肺和肝脏相比，对致癌的作用 由多核芳香烃组成。更全面地了解 多核中最重要的结构特征和反应 芳香烃致癌可能最终导致治疗方法的出现 预防某些人类癌症目前被认为是 由这类化学致癌物引起的。

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.