DNA MODIFICATIONS BY PYRUVALDEHYDE

丙酮醛对 DNA 的修饰

• 批准号: 3187014
• 负责人: CHING-JER CHANG
• 金额: $ 12万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-12-01 至 1993-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3187014
• 关键词: DNA; adduct; chemical carcinogen; enzyme mechanism; glyoxal; high performance liquid chromatography; molecular site; nuclear magnetic resonance spectroscopy; tissue /cell culture

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.

该提案旨在开发一种可靠的方法来实现基本 生物醛遗传毒性作用的机制研究 分子水平。 主要努力集中于解开 相互作用的结构特异性、动力学和定量 体外丙酮醛与 DNA。 反应位点和产物 最初将使用解决方案通过直接方法研究分布 和固态碳13核磁共振波谱，然后 通过使用酶降解的间接方法，然后进行高 高效液相色谱分离和定量。 该提案的成功将为体内研究铺平道路 潜在诱变/致癌 DNA 加合物的形成和修复 培养物和动物中的细胞。 生物分析方法开发于 该提议也可以应用于 DNA 修饰的研究 其他二羰基化合物。 它将提供分子基础 了解二羰基的基本诱变/致癌机制 化合物。