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.

自由基代谢产物与DNA的相互作用一直是研究的一个重要领域 感兴趣和猜测，但以前的电子自旋共振（ESR） 对这一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 用自旋共振技术研究了脱氧核糖核苷酸 诱捕采用自旋捕集器t-亚硝基丁烷捕集次级产物 由羟基自由基与这些反应形成的自由基 个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， 与使用X射线或伽马射线的作者先前工作的相关性 照射以产生羟基自由基。硫代巴比妥酸测定 也被用来监测核苷酸产生的损害， 芬顿系统。这些结果与自旋定性一致 诱捕研究