Oxidation of DNA bases, deoxyribonucleosides and homopolymers by peroxyl radicals.

Oxidation of DNA bases, deoxyribonucleosides and homopolymers by peroxyl radicals.
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DOI：
10.1042/bj3350233
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发表时间：
1998-10
期刊：
The Biochemical journal
影响因子：
--
通讯作者：
T. Simandan;Jing Sun;Thomas A. Dix
T. Simandan;Jing Sun;Thomas A. Dix
中科院分区：
其他
文献类型：
--
作者：
T. Simandan;Jing Sun;Thomas A. Dix

文献摘要

相似文献

DNA碱基氧化被认为是与人类疾病发生和发展相关的关键事件。过氧自由基（ROO）是细胞中发现的重要氧化剂，其与DNA碱基反应的能力尚未得到广泛的研究。在本文中，产品产生的ROO。用气相色谱/质谱法测定DNA碱基的氧化情况，并与标准品进行比较。ROO。自由基将腺嘌呤和鸟嘌呤氧化为8-羟基衍生物，被认为是细胞中羟基自由基氧化的生物标志物。ROO。自由基也将腺嘌呤氧化为羟胺，这是一种以前未发现的产物。ROO。自由基将胞嘧啶和胸腺嘧啶氧化为细胞氧化损伤形成的单羟基和二羟基衍生物。相同的ROO。当暴露为脱氧核糖核苷、单均聚物和碱基对二均聚物时，观察到每个碱基的氧化谱。这些结果对于开发、利用和解释与疾病发生和繁殖相关的DNA碱基衍生的氧化损伤生物标志物具有重要意义，并支持细胞DNA中产生n -氧化碱基的致突变潜力需要仔细评估的观点。腺嘌呤羟胺被认为是检测ROO活性的特异性分子探针。在细胞系统中。
DNA base oxidation is considered to be a key event associated with disease initiation and progression in humans. Peroxyl radicals (ROO. ) are important oxidants found in cells whose ability to react with the DNA bases has not been characterized extensively. In this paper, the products resulting from ROO. oxidation of the DNA bases are determined by gas chromatography/MS in comparison with authentic standards. ROO. radicals oxidize adenine and guanine to their 8-hydroxy derivatives, which are considered biomarkers of hydroxyl radical (HO.) oxidations in cells. ROO. radicals also oxidize adenine to its hydroxylamine, a previously unidentified product. ROO. radicals oxidize cytosine and thymine to the monohydroxy and dihydroxy derivatives that are formed by oxidative damage in cells. Identical ROO. oxidation profiles are observed for each base when exposed as deoxyribonucleosides, monohomopolymers and base-paired dihomopolymers. These results have significance for the development, utilization and interpretation of DNA base-derived biomarkers of oxidative damage associated with disease initiation and propagation, and support the idea that the mutagenic potential of N-oxidized bases, when generated in cellular DNA, will require careful evaluation. Adenine hydroxylamine is proposed as a specific molecular probe for the activity of ROO. in cellular systems.