Cooke Marcus S, Evans Mark D, Dizdaroglu Miral, Lunec Joseph
Oxidative Stress Group, Department of Clinical Biochemistry, University of Leicester, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, LE2 7LX, UK.
FASEB J. 2003 Jul;17(10):1195-214. doi: 10.1096/fj.02-0752rev.
Oxidative DNA damage is an inevitable consequence of cellular metabolism, with a propensity for increased levels following toxic insult. Although more than 20 base lesions have been identified, only a fraction of these have received appreciable study, most notably 8-oxo-2'deoxyguanosine. This lesion has been the focus of intense research interest and been ascribed much importance, largely to the detriment of other lesions. The present work reviews the basis for the biological significance of oxidative DNA damage, drawing attention to the multiplicity of proteins with repair activities along with a number of poorly considered effects of damage. Given the plethora of (often contradictory) reports describing pathological conditions in which levels of oxidative DNA damage have been measured, this review critically addresses the extent to which the in vitro significance of such damage has relevance for the pathogenesis of disease. It is suggested that some shortcomings associated with biomarkers, along with gaps in our knowledge, may be responsible for the failure to produce consistent and definitive results when applied to understanding the role of DNA damage in disease, highlighting the need for further studies.
氧化性DNA损伤是细胞代谢不可避免的结果，在受到毒性损伤后其水平往往会升高。尽管已鉴定出20多种碱基损伤，但其中只有一小部分得到了充分研究，最显著的是8-氧代-2'-脱氧鸟苷。这种损伤一直是深入研究的焦点，并被赋予了很大的重要性，这在很大程度上损害了对其他损伤的研究。本研究综述了氧化性DNA损伤生物学意义的基础，提请注意具有修复活性的多种蛋白质以及一些未被充分考虑的损伤效应。鉴于有大量（往往相互矛盾）的报告描述了测量氧化性DNA损伤水平的病理状况，本综述批判性地探讨了这种损伤在体外的意义与疾病发病机制相关的程度。有人认为，与生物标志物相关的一些缺点以及我们知识上的空白，可能是在应用于理解DNA损伤在疾病中的作用时未能产生一致和明确结果的原因，这突出了进一步研究的必要性。
