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的相互作用已成为主要区域 感兴趣和猜测，但先前的电子自旋共振（ESR） 对该领域的调查非常有限。反应 羟基自由基，由芬顿系统产生，嘧啶产生 使用自旋的ESR技术研究了脱氧核糖核苷酸 陷阱。旋转陷阱T-硝基丁烷用于捕获次级 由羟基自由基与这些反应形成的自由基 核苷酸。此处介绍的结果显示了对 胸苷，2-脱氧胞苷5-单磷酸和2-脱氧尿苷 5单磷酸盐产生了核苷酸来源的自由基。结果 表明OH激进攻击主要发生在碳碳 嘧啶碱的双键。 ESR研究表明很好 与使用X-或Gamma-ray的作者制作的先前作品相关 辐射以产生羟基自由基。硫巴比妥酸测定法 还用于监测通过 芬顿系统。这些结果表明与旋转的定性一致 捕获研究。