EXOCYCLIC ADDUCTS--SITE-SPECIFIC MUTAGENESIS

这项研究的目的是确定突变谱的 在哺乳动物细胞和细菌中，当环外加合物 在特定的基因组位点引入，并描绘重组 事件，因为它们涉及由这样的加合物产生的诱变。 DNA加合物可以通过修复酶的协同作用而被去除， 整个基因组。 当这一过程未完成时， DNA复制中的错误导致突变。 我们打算投资- 在DNA修复的几个方面，因为它涉及到结构和 环外加合物的功能。 我们已经开发了实验系统，使用基于SV 40的穿梭质粒 载体，通过该载体，可以选择DNA加合物的诱变谱， 测定 这种方法使我们能够检查的序列特异性 突变反应，特别是关于“热点”和原- 致癌基因 使用这些系统，反映了前向诱变事件 产生的单一种类的DNA加合物，并通过关联我们的研究 通过分子模拟和2D-NMR实验的结果，我们希望 定义有助于阐明 化学诱变的机制，并可能预测诱变效应 某些化学致癌物。

The objectives of this research are to determine the mutational spectra of lesions produced in mammalian cells and bacteria when exocyclic adducts are introduced at specific genomic sites and to delineate recombinational events as they relate to mutagenesis produced by such adducts. DNA adducts may be removed by the concerted action of repair enzymes acting throughout the genome. When this process is incomplete, the stage is set for errors in DNA replication that lead to mutation. We intend to inves- tigate several aspects of DNA repair as it relates to the structure and function of exocyclic adducts. We have developed experimental systems, using SV40-based shuttle plasmid vectors, by which the mutagenic spectra of selected DNA adducts can be determined. This approach allows us to examine the sequence specificity of mutational reactions with particular reference to "hot spots" and proto- oncogenes. Using these systems, which reflect forward mutagenic events produced by a single species of DNA adduct and by correlating our studies with the results of molecular modeling and 2D-NMR experiments, we hope to define structure-activity relationships that will assist in elucidating mechanisms of chemical mutagenesis and, possibly, predict mutagenic effects for certain classes of chemical carcinogens.