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标题：Oxidative Stress-Induced Carcinogenesis and Its Prevention Guest Editor: Shinya Toyokuni Sources of Extracellular, Oxidatively-Modified DNA Lesions: Implications for Their Measurement in Urine
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作者：Marcus S. Cooke ; Paul T. Henderson ; Mark D. Evans 等
期刊名称：Journal of Clinical Biochemistry and Nutrition
印刷版ISSN：0912-0009
电子版ISSN：1880-5086
出版年度：2009
卷号：45
期号：3
页码：255-270
DOI：10.3164/jcbn.SR09-41
出版社：The Society for Free Radical Research Japan
摘要：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.
关键词：DNA damage;urine;oxidative stress;DNA repair;cell death