Valavanidis Athanasios, Vlachogianni Thomais, Fiotakis Constantinos
Department of Chemistry, University of Athens, University Campus Zografou, Greece.
J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2009 Apr;27(2):120-39. doi: 10.1080/10590500902885684.
There is extensive experimental evidence that oxidative damage permanently occurs to lipids of cellular membranes, proteins, and DNA. In nuclear and mitochondrial DNA, 8-hydroxy-2' -deoxyguanosine (8-OHdG) or 8-oxo-7,8-dihydro-2' -deoxyguanosine (8-oxodG) is one of the predominant forms of free radical-induced oxidative lesions, and has therefore been widely used as a biomarker for oxidative stress and carcinogenesis. Studies showed that urinary 8-OHdG is a good biomarker for risk assessment of various cancers and degenerative diseases. The most widely used method of quantitative analysis is high-performance liquid chromatography (HPLC) with electrochemical detection (EC), gas chromatography-mass spectrometry (GC-MS), and HPLC tandem mass spectrometry. In order to resolve the methodological problems encountered in measuring quantitatively 8-OHdG, the European Standards Committee for Oxidative DNA Damage was set up in 1997 to resolve the artifactual oxidation problems during the procedures of isolation and purification of oxidative DNA products. The biomarker 8-OHdG or 8-oxodG has been a pivotal marker for measuring the effect of endogenous oxidative damage to DNA and as a factor of initiation and promotion of carcinogenesis. The biomarker has been used to estimate the DNA damage in humans after exposure to cancer-causing agents, such as tobacco smoke, asbestos fibers, heavy metals, and polycyclic aromatic hydrocarbons. In recent years, 8-OHdG has been used widely in many studies not only as a biomarker for the measurement of endogenous oxidative DNA damage but also as a risk factor for many diseases including cancer.
有大量实验证据表明,细胞膜中的脂质、蛋白质和DNA会发生永久性氧化损伤。在细胞核DNA和线粒体DNA中,8-羟基-2'-脱氧鸟苷(8-OHdG)或8-氧代-7,8-二氢-2'-脱氧鸟苷(8-oxodG)是自由基诱导的氧化损伤的主要形式之一,因此被广泛用作氧化应激和致癌作用的生物标志物。研究表明,尿8-OHdG是评估各种癌症和退行性疾病风险的良好生物标志物。最常用的定量分析方法是高效液相色谱(HPLC)与电化学检测(EC)、气相色谱-质谱联用(GC-MS)以及HPLC串联质谱。为了解决定量测量8-OHdG时遇到的方法学问题,1997年成立了欧洲氧化DNA损伤标准委员会,以解决氧化DNA产物分离和纯化过程中的人为氧化问题。生物标志物8-OHdG或8-oxodG一直是测量内源性DNA氧化损伤效应以及作为致癌作用起始和促进因素的关键标志物。该生物标志物已被用于估计人类接触致癌物质(如烟草烟雾、石棉纤维、重金属和多环芳烃)后DNA的损伤情况。近年来,8-OHdG不仅作为测量内源性氧化DNA损伤的生物标志物,而且作为包括癌症在内的许多疾病的风险因素,在许多研究中得到了广泛应用。