ROS-induced Nucleic Acid Damage

ROS诱导的核酸损伤

• 批准号: 6637068
• 负责人: Yinsheng Wang
• 金额: $ 17.07万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6637068
• 关键词: DNA damage; adduct; chemical models; free radical oxygen; gene mutation; mass spectrometry; molecular dynamics; nucleic acid structure; oxidative stress; technology /technique development; thermodynamics

DESCRIPTION (provided by applicant): Reactive oxygen species (ROS) are generated in cells either by aerobic metabolism or by exposure to ionizing radiation and other oxidizing agents. They can damage cellular components by a radical-mediated mechanism. The resulting damaged products of nucleic acids have been implicated in cancer, neurological disorder, and natural processes of aging. Here we propose to develop sensitive mass spectrometric methods to characterize the structures and to quantify the amounts of oxidative DNA and RNA lesions, and there is a strong prospect that we will find new lesions. We also propose to study the chemical and biological properties of those oxidative lesions via mass spectrometry. Molecular modeling, organic synthesis, and other spectroscopic techniques will also be employed to answer those questions. The outcome of the research proposed here will provide better understanding of the biological consequences of oxidative damage on nucleic acids by ROS and their implications in human health.

描述（由申请人提供）：活性氧（ROS）通过有氧代谢或暴露于电离辐射和其他氧化剂在细胞中产生。它们可以通过自由基介导的机制破坏细胞成分。由此产生的核酸受损产物与癌症、神经系统疾病和自然衰老过程有关。在这里，我们建议开发灵敏的质谱方法来表征结构和定量的氧化DNA和RNA病变的量，有一个强大的前景，我们将发现新的病变。我们还建议通过质谱法研究这些氧化损伤的化学和生物学性质。分子模拟、有机合成和其他光谱技术也将被用来回答这些问题。这里提出的研究结果将提供更好地了解ROS对核酸氧化损伤的生物学后果及其对人类健康的影响。