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的相互作用一直是一个重要的研究领域。 主要领域的兴趣和猜测，但以前的电子自旋 共振（ESR）研究这一领域已经非常有限。 通过芬顿系统产生的羟基自由基的反应， 与嘧啶脱氧核糖核苷酸的ESR研究 自旋捕获技术。 自旋阱t-亚硝基丁烷是 用于捕获由反应形成的次级自由基， 羟基与这些核苷酸。 呈现的结果 这里显示羟基自由基攻击胸苷，2-脱氧胞苷 5-产生的2-脱氧尿苷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， 自由基攻击主要发生在碳-碳双键上 嘧啶碱基的键。 ESR研究显示， 与使用x- or的作者以前的工作的相关性 γ射线照射产生羟基自由基。 一 硫代巴比妥酸法检测损伤程度 通过芬顿系统生成核苷酸。 这些结果 与自旋捕获研究定性一致。