MOLECULAR EVENTS IN CHEMICAL CARCINOGENESIS

目标仍然是阐明分子机制 化学致癌物的作用。 这笔赠款将有助于 跨学科的方法，这是必要的，因为复杂的， 致癌的多阶段过程。 拟议的研究将在 一个逻辑连续体，包括以下主要主题：1） 化学和立体化学基础的共价键合化学 2）阐明DNA构象的变化， 这些化学修饰的结果，以及对它们的研究， 功能意义，3）高度特异性和 灵敏的免疫测定，以促进化学品的分子研究 致癌作用和4）分子遗传学研究旨在评估 DNA中产生的结构变化可能是由于 化学致癌物的修饰，不仅可以诱导点突变， 但也有复杂的基因组效应，包括基因扩增， 基因表达改变和基因转座（项目E）。 这 综合方法应提供对基础知识的根本见解 化学致癌物的作用机制，从而提供合理的 致癌物检测、风险外推和癌症 预防

The objective continues to be the elucidation of the molecular mechanisms of action of chemical carcinogens. This grant will facilitate an interdisciplinary approach, which is required in view of the complexity of the multistage process of carcinogenesis. The proposed studies will follow a logical continuum that includes the following major topics: 1) the chemistry and stereochemistry underlying the covalent binding of chemical carcinogens to DNA, 2) elucidation of the changes in DNA conformation that result from these chemical modifications, as well as studies on their functional significance, 3) the development of highly specific and sensitive immunoassays to facilitate molecular studies on chemical carcinogenesis and 4) molecular genetic studies designed to assess the possibility that the structural changes produced in DNA, as a result of modification by chemical carcinogens, can induce, not only point mutations, but also complex genomic effects, including gene amplification, stable alterations in gene expression and gene transposition (Project E). This integrated approach should provide fundamental insights into basic mechanisms of action of chemical carcinogens and thus provide rational approaches to carcinogen detection, risk extrapolation and cancer prevention.