REACTION OF FREE RADICAL METABOLITES WITH DNA

自由基代谢物与 DNA 的反应

• 批准号: 3876931
• 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/3876931
• 关键词: DNA; biophysics; covalent bond; deoxycytidine; deoxyuridine; drug interactions; electron spin resonance spectroscopy; free radicals; hydroxyl group; nitroso compounds; oxidation reduction reaction; thiopental; 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主要领域 引起人们的兴趣和猜测，但之前的电子自旋共振（ESR） 该领域的调查非常有限。的反应 羟基自由基，由芬顿系统与嘧啶产生 使用自旋 ESR 技术研究脱氧核糖核苷酸 诱捕。自旋捕获叔亚硝基丁烷用于捕获二次 羟基自由基与这些自由基反应形成的自由基 核苷酸。这里给出的结果表明羟基自由基攻击 胸苷、2-脱氧胞苷、5-单磷酸和2-脱氧尿苷 5-单磷酸产生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 嘧啶碱基的双键。 ESR 研究显示出良好的 与使用 X 射线或伽马射线的作者之前所做的工作的相关性 照射产生羟基自由基。硫代巴比妥酸测定 还用于监测核苷酸对核苷酸产生的损伤 芬顿系统。这些结果表明与旋转定性一致 诱捕研究。