Cooke Marcus S, Lunec Joseph, Evans Mark D
Oxidative Stress Group, Department of Clinical Biochemistry, University of Leicester, Leicester Royal Infirmary, Leicester, UK.
Free Radic Biol Med. 2002 Dec 15;33(12):1601-14. doi: 10.1016/s0891-5849(02)01146-2.
Oxidative DNA damage has been implicated to be important in the pathogenesis of many diseases, including cancer and heart disease. The assessment of damage in various biological matrices, such as DNA, serum, and urine, is vital to understanding this role and subsequently devising intervention strategies. Despite the numerous techniques to measure oxidative DNA damage products in urine, it remains unclear what these measurements truly represent. Sources of urinary lesions may include the diet, cell death, and, of most interest, DNA repair. Were it possible to exclude the two former contributions, a noninvasive assay for DNA repair would be invaluable in the study of DNA damage and disease. This review highlights that, although progress has been made, significant work remains. Diet, cell death, and repair need continued examination to further elucidate the kinetics of lesion formation and clearance in vivo. Studies from our laboratory and others are making appreciable progress towards the interpretation of urinary lesion measurements along with the development of urinary assays to evaluate DNA repair. Upon establishment of these details, urinary oxidative DNA damage measurements may become more than a reflection of generalized oxidative stress.
氧化DNA损伤被认为在包括癌症和心脏病在内的许多疾病的发病机制中起着重要作用。评估各种生物基质(如DNA、血清和尿液)中的损伤对于理解这一作用并随后制定干预策略至关重要。尽管有许多技术可用于测量尿液中的氧化DNA损伤产物,但这些测量结果究竟代表什么仍不清楚。尿液损伤的来源可能包括饮食、细胞死亡,以及最受关注的DNA修复。如果能够排除前两者的影响,那么一种用于DNA修复的非侵入性检测方法在DNA损伤和疾病研究中将具有极高的价值。这篇综述强调,尽管已经取得了进展,但仍有大量工作要做。饮食、细胞死亡和修复需要持续研究,以进一步阐明体内损伤形成和清除的动力学。我们实验室和其他机构的研究在解释尿液损伤测量结果以及开发评估DNA修复的尿液检测方法方面取得了显著进展。一旦确定了这些细节,尿液氧化DNA损伤测量可能不仅仅是对全身性氧化应激的反映。