DNA MODIFICATIONS BY PYRUVALDEHYDE

该提案旨在制定一种可靠的基本方法 生物醛遗传毒性效应的机制研究 分子水平。主要的努力集中在解开 相互作用的结构特异性、动力学和量化 丙酮醛与DNA的体外结合。反应部位和产物 最初将通过使用解决方案的直接方法研究分布 和固态碳13核磁共振波谱，然后 通过使用酶降解然后高密度的间接方法 高效液相色谱分离和定量。 这一建议的成功将为体内研究奠定基础。 潜在的致突变/致癌DNA加合物的形成和修复 培养和动物中的细胞。年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，为 了解二酮基致突变/致癌的基本机制 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.