Sources of extracellular, oxidatively-modified DNA lesions: implications for their measurement in urine.
Sources of extracellular, oxidatively-modified DNA lesions: implications for their measurement in urine.
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DOI：
10.3164/jcbn.sr09-41
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发表时间：
2009-11
影响因子：
2.4
通讯作者：
Evans MD
中科院分区：
文献类型：
--
作者：
Cooke MS;Henderson PT;Evans MD
DNA氧化损伤在各种主要疾病（心血管疾病、神经退行性疾病、癌症）的病因学中所起的作用有着坚实的机制基础。在分子流行病学背景下，需要强大的、经过验证的生物标志物来测量氧化损伤，澄清与氧化应激相关的风险，提高我们对氧化应激在健康和疾病中的作用的理解，并测试干预策略来改善氧化应激。在DNA氧化的尿液生物标志物中，8-氧-7,8-二氢-2'-脱氧鸟苷（8-oxodG）是研究最多的。然而，有许多因素阻碍了我们对尿液中这种病变的测量实际代表的完整理解。DNA修复被认为是尿8-氧化氧化g水平的主要因素，尽管精确的途径尚未得到证实，加上细胞更新和饮食的可能贡献是可能的混杂因素。最近，有证据表明，至少在快速分裂的细胞中，8-oxodG和8-oxoGua的核苷酸回收可以显著提高DNA和RNA中的8-oxoG水平。这一新的观察结果可能进一步混淆了8-氧瓜a或8-氧odg及其核碱基等同物8-氧鸟嘌呤在尿液中的浓度仅仅是DNA修复的结果的结论。需要进一步的研究来确定代谢、疾病和饮食对尿液中氧化核酸及其代谢物的相对贡献，以便使尿液分析成为了解人类疾病的更好工具。
There is a robust mechanistic basis for the role of oxidation damage to DNA in the aetiology of various major diseases (cardiovascular, neurodegenerative, cancer). Robust, validated biomarkers are needed to measure oxidative damage in the context of molecular epidemiology, to clarify risks associated with oxidative stress, to improve our understanding of its role in health and disease and to test intervention strategies to ameliorate it. Of the urinary biomarkers for DNA oxidation, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is the most studied. However, there are a number of factors which hamper our complete understanding of what meausrement of this lesion in urine actually represents. DNA repair is thought to be a major contributor to urinary 8-oxodG levels, although the precise pathway(s) has not been proven, plus possible contribution from cell turnover and diet are possible confounders. Most recently, evidence has arisen which suggests that nucleotide salvage of 8-oxodG and 8-oxoGua can contribute substantially to 8-oxoG levels in DNA and RNA, at least in rapidly dividing cells. This new observation may add an further confounder to the conclusion that 8-oxoGua or 8-oxodG, and its nucleobase equivalent 8-oxoguanine, concentrations in urine are simply a consequence of DNA repair. Further studies are required to define the relative contributions of metabolism, disease and diet to oxidised nucleic acids and their metabolites in urine in order to develop urinalyis as a better tool for understanding human disease.