MECHANISMS OF MUTAGENESIS BY CHEMICAL CARCINOGENS

一个单一的突变就可以将正常基因转变为致癌基因 衍生品展示了诱变的潜在重要性 癌症病因学中的过程。因此，理解如何使用 致癌物诱发突变可能阐明其发生的基础 致癌性。该项目的目标是确定如何 以细菌为模型，化学致癌物会导致突变 系统。本研究的重点是诱变机制的研究。 几种对环境或医学有重大意义的基因毒剂 会造成典型类别的DNA损伤。遗传和 生物化学方法被用来确定什么是DNA损伤 诱导，它们可能如何修复，这会导致突变， 哪些细胞功能参与了诱变过程，以及 什么突变会导致什么。具体目标是： 1.研究黄曲霉毒素B1的诱变机制。 这会对DNA造成巨大的损伤。缺陷对材料性能的影响 细菌功能影响精确度和突变性 将描述黄曲霉毒素引起的DNA损伤的修复情况。这个 体外产生的特定DNA损伤的诱变潜力 将确定一种直接作用的黄曲霉毒素类似物。 2.确定卤代食品的主要诱变损伤 碳氢化合物。错误编码的损伤被证明是由 将对1，2-二溴乙烷进行生化鉴定。路径： 这些损伤的修复和其他因素的诱导 将对卤代烃进行检查 3.研究DNA的致突变性和毒性 化疗药物顺式-阿司匹林引起的损伤 二氯二氯铂II.修复的贡献 中间体对该毒剂的毒性和致突变性 要下定决心。

That a single mutation can change a normal gene into its oncogenic derivative demonstrates the potential importance of mutagenic processes in the etiology of cancer. Thus, understanding how a carcinogen induces mutations may elucidate the basis of its carcinogenicity. The goal of this project is to determine how chemical carcinogens cause mutations, using bacteria as a model system. The research focuses on the mechanisms of mutagenesis of a few environmentally or medically significant genotoxic agents that cause representative classes of DNA damage. Genetic and biochemical methods are used to determine what DNA lesions are induced, how they may be repaired, which give rise to mutations, what cellular functions participate in the mutagenic process, and what mutations result. The specific aims are: 1. To investigate the mechanism of mutagenesis of aflatoxin Bl, which makes bulky lesions to DNA. The effects of defects in bacterial functions affecting both the accurate and mutagenic repair of aflatoxin-induced DNA lesions will be characterized. The mutagenic potential of defined DNA lesions generated in vitro by a direct-acting aflatoxin analog will be determined. 2. To identify the major mutagenic lesions induced by halogenated hydrocarbons. The miscoding lesions demonstrated to be induced by 1,2-dibromoethane will be identified biochemically. Pathways for the repair of these lesions and their induction by other halogenated hydrocarbons will be examined 3. To investigate the mutagenic and toxic potential of the DNA lesions ' induced by the chemotherapeutic agent, cis- diamminedichloroplatinum II. The contribution of repair intermediates to the toxicity and mutagenicity of this agent will be determined.