DNA MODIFICATIONS BY PYRUVALDEHYDE

该建议旨在为基本的 生物醛的遗传毒性作用机制研究 分子水平。 主要的努力集中在解开 结构特异性，动力学和定量的相互作用， 异戊醛与DNA的体外杂交。 反应位点和产物 分布将首先通过使用解决方案的直接方法进行研究 和固态碳13核磁共振光谱，然后 通过使用酶降解的间接方法， 高效液相色谱分离和定量。 这一提议的成功将为以下方面的体内研究铺平道路 潜在致突变/致癌DNA加合物的形成和修复 培养细胞和动物。 开发的生物分析方法 这一建议也可以应用于DNA修饰的研究， 其他二羰基化合物。 它将提供分子基础， 了解二羰基的基本致突变/致癌机制 化合物.

This proposal is aimed at developing a reliable approach for basic mechanistic studies on the genotoxic effect of biological aldehyde at the molecular level. The primary effort is focused on unraveling the structural specificity, dynamics and quantitation of the interactions of pyruvaldehyde with DNA in vitro. The sites of reaction and the product distribution will be initially studied by a direct approach using solution and solid-state carbon-13 nuclear magnetic resonance spectroscopy, and then by an indirect approach using enzymic degradation followed by high performance liquid chromatographic separation and quantitation. The success of this proposal will pave the way for the in vivo studies on the formation and repair of potential mutagenic/carcinogenic DNA adducts in cells in culture and animals. The bioanalytical methodologies developed in this proposal can also be applied to the study of DNA modifications by other dicarbonyl compounds. It will provide the molecular basis for understanding the basic mutagenic/carcinogenic mechanisms of dicarbonyl compounds.