OXIDATIVE DNA DAMAGE AND MUTATION IN CELLS

细胞中 DNA 氧化损伤和突变

• 批准号: 6200945
• 负责人: RAYMOND J MONNAT
• 金额: $ 15.89万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6200945
• 关键词: Aves; DNA damage; Werner's syndrome; adduct; age difference; aging; antioxidants; cytogenetics; gene mutation; genetic markers; genetically modified animals; human tissue; kidney; laboratory mouse; membrane potentials; mitochondrial DNA; oxidative stress; species difference

The longterm goal of the proposed research is to determine the contribution of oxidative DNA damage-associated mutation to aging and to the pathogenesis of age-associated disease. The specific aims of the proposed research focus on the molecular markers of oxidative DNA damage and mutation in human, mouse and avian tissues that have different intrinsic antioxidant defense capacities, or in which antioxidant defense capacity has been experimentally modified. We will determine levels of 2 oxidative DNA damage adducts (5-OH-dC and 8-oxo-dG) and the frequency of oxidative damage-associated CC to TT mutations and of randomly distributed mutations in mtDNA from human, mouse and avian cells. We will also determine the frequency and molecular spectrum of HPRT mutations in human and mouse kidney. The explicit hypothesis we will test is that enhanced antioxidant defense capacity will be associated with lower levels of both oxidative DNA damage and mutation in vivo. Results of this work will allow us to determine the relationship of mtDNA damage and mutation to organellar dysfunction, and the spectrum of nuclear DNA mutations as a function of age, species and antioxidant defense capacity.

拟议研究的长期目标是确定 氧化性DNA损伤相关的突变对衰老和对 与年龄相关疾病的发病机理。特定目标 建议的研究重点是氧化DNA损伤的分子标记 和具有不同的人，小鼠和鸟类组织中的突变 内在的抗氧化剂防御能力或抗氧化剂防御能力 容量已经过实验修改。我们将确定2个 氧化DNA损伤加合物（5-OH-DC和8-oxo-DG）和频率 与TT突变和随机分布的氧化损伤相关的CC 来自人，小鼠和鸟类细胞的mtDNA突变。我们也会 确定人类HPRT突变的频率和分子光谱 和鼠标肾脏。我们将检验的明确假设是 抗氧化剂防御能力将与两者的较低水平有关 氧化性DNA损伤和体内突变。这项工作的结果将允许 我们确定mtDNA损伤和突变与 细胞器功能障碍，核DNA突变的光谱作为一个 年龄，物种和抗氧化剂防御能力的功能。