REACTION OF FREE RADICAL METABOLITES WITH DNA

自由基代谢物与 DNA 的反应

• 批准号: 3918693
• 负责人: R P MASON
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3918693
• 关键词: DNA; biophysics; chlorpromazine; deoxycytidine; deoxyuridine; drug interactions; electron spin resonance spectroscopy; free radicals; hydroxyl group; molecular biology; oxidation reduction reaction; thymidine

The interaction of free radical metabolites with DNA has been a major area of interest and speculation, but previous electron spin resonance (ESR) investigations of this area have been very limited. The reaction of the hydroxyl radical, generated by a Fenton system, with pyrimidine deoxyribonucleotides was investigated using the ESR technique of spin trapping. The spin trap t-nitrosobutane was employed to trap secondary radicals formed by the reaction of the hydroxyl radical with these nucleotides. The results presented here show the hydroxyl radical attack on thymidine, 2-deoxycytidine 5-monophosphate and 2-deoxyuridine 5-monophosphate produced nucleotide-derived free radicals. The results indicate that .OH radical attack occurs predominantly at the carbon-carbon double bond of the pyrimidine base. The ESR studies showed a good correlation with previous work produced by authors who used x- or gamma-ray irradiation to generate the hydroxyl radical. A thiobarbituric acid assay was also used to monitor the damage produced to the nucleotides by the Fenton system. These results showed qualitative agreement with the spin trapping studies.

自由基代谢物与 DNA 的相互作用一直是 感兴趣和猜测的主要领域，但之前的电子自旋 该领域的共振（ESR）研究非常有限。 由芬顿系统产生的羟基自由基的反应， 使用 ESR 研究了嘧啶脱氧核糖核苷酸 自旋捕获技术。 自旋陷阱叔亚硝基丁烷是 用于捕获由反应形成的二次自由基 羟基自由基与这些核苷酸。 呈现的结果 这里显示羟基自由基对胸苷、2-脱氧胞苷的攻击 产生5-单磷酸和2-脱氧尿苷5-单磷酸 核苷酸衍生的自由基。 结果表明.OH 自由基攻击主要发生在碳-碳双原子上 嘧啶碱基的键。 ESR 研究显示出良好的 与使用 x- 或的作者之前所做的工作的相关性 伽马射线照射产生羟基自由基。 一个 硫代巴比妥酸测定也用于监测损害 通过芬顿系统产生核苷酸。 这些结果 显示出与自旋捕获研究的定性一致性。