Loft S, Poulsen H E
Department of Pharmacology, University of Copenhagen, Denmark.
Acta Biochim Pol. 1998;45(1):133-44.
DNA is constantly damaged and repaired in living cells. The repair products of the oxidative DNA lesions, i.e. oxidised nucleosides and bases, are poor substrates for the enzymes involved in nucleotide synthesis, are fairly water soluble, and generally excreted into the urine without further metabolism. Among the possible products, 8-oxo-2'-deoxyguanosine, 8-oxoguanine, thymine glycol, thymidine glycol and, 5-hydroxymethyluracil have so far been identified in urine. It should be emphasised that the excretion of the repair products in urine represents the average rate of damage in the total body whereas the level of oxidised bases in nuclear DNA is a concentration measurement in that specific tissue/cells in the moment of sampling. The rate of oxidative DNA modifications has been studied in humans by means of the repair products as urinary biomarkers, particularly with respect to 8-oxo-2'-deoxyguanosine. The data obtained so far indicate that the important determinants of the oxidative damage rate include tobacco smoking, oxygen consumption and some inflammatory diseases whereas diet composition, energy restriction and antioxidant supplements have but a minimal influence, possibly with the exception of yet unidentified phytochemicals, e.g. from cruciferous vegetables. The data are consistent with the experimentally based notion that oxidative DNA damage is an important mutagenic and apparently carcinogenic factor. However, the proof of a causal relationship in humans is still warranted. In the future the use of biomarkers may provide this evidence and allow further investigations on the qualitative and quantitative importance of oxidative DNA modification and carcinogenesis in man, as well as elucidate possible preventive measures.
在活细胞中，DNA不断受到损伤并得到修复。氧化性DNA损伤的修复产物，即氧化核苷和碱基，是参与核苷酸合成的酶的不良底物，具有相当的水溶性，通常不经进一步代谢就排泄到尿液中。在可能的产物中，8-氧代-2'-脱氧鸟苷、8-氧代鸟嘌呤、胸腺嘧啶乙二醇、胸苷乙二醇和5-羟甲基尿嘧啶目前已在尿液中被鉴定出来。应该强调的是，尿液中修复产物的排泄代表了全身的平均损伤率，而核DNA中氧化碱基的水平是采样时该特定组织/细胞中的浓度测量值。通过将修复产物作为尿液生物标志物，对人类氧化性DNA修饰的速率进行了研究，特别是针对8-氧代-2'-脱氧鸟苷。迄今为止获得的数据表明，氧化损伤率的重要决定因素包括吸烟、耗氧量和一些炎症性疾病，而饮食组成、能量限制和抗氧化剂补充剂的影响极小，可能除了尚未确定的植物化学物质，例如十字花科蔬菜中的物质。这些数据与基于实验的观点一致，即氧化性DNA损伤是一个重要的诱变因素，显然也是致癌因素。然而，在人类中因果关系的证据仍有待证实。未来，生物标志物的使用可能会提供这一证据，并允许对氧化性DNA修饰和致癌作用在人类中的定性和定量重要性进行进一步研究，以及阐明可能的预防措施。
