Biomarkers of oxidative damage to DNA and repair
Biomarkers of oxidative damage to DNA and repair
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DOI：
10.1042/bst0361071
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发表时间：
2008-10-01
影响因子：
3.9
通讯作者：
Moller, Peter
中科院分区：
文献类型：
--
作者：
Loft, Steffen;Danielsen, Pernille Hogh;Moller, Peter
氧化应激诱导的DNA损伤包括许多损伤，其中许多是突变的，在癌症和衰老中具有多种作用。许多病变在提取和消化DNA后，已经用基于MS的方法进行了表征。这些制备步骤可能会导致假碱基氧化，这在彗星试验等方法中发生的可能性较小，这些方法基于DNA链在修饰碱基上的缺口，但提供的特异性较低。欧洲DNA氧化损伤标准委员会得出结论，研究最广泛的损伤8-oxodG(8-oxo-7，8-二氢-2‘脱氧鸟苷)在细胞DNA中的真实水平在每10(6)dG碱基中有0.5到5个损伤。DNA氧化损伤的碱基切除修复可以通过基于带有损伤的寡核苷酸的缺口分析或彗星实验、通过mRNA表达水平或在例如OGG1(8-oxoguanine DNA糖基酶1)的情况下通过基因分型来评估，OGG1(8-oxoguanine DNA Glycoylase 1)负责8-oxodG的修复。DNA或核苷酸库中的修复产物，如8-oxodG，排入尿液可以用基于MS的方法进行评估，通常反映损伤的速度。实验和基于人群的研究表明，许多环境因素，包括颗粒物空气污染，会对DNA造成氧化损伤，而富含水果和蔬菜的饮食或抗氧化剂补充剂可能会降低这种水平并促进修复。在队列环境中，尿8-oxodG、OGG1基因和表达与癌症风险相关，而在病例对照环境中，损伤、修复或尿液排泄水平的改变可能是结果，而不是疾病的原因。
Oxidative-stress-induced damage to DNA includes a multitude of lesions, many of which are mutagenic and have multiple roles in cancer and aging. Many lesions have been characterized by MS-based methods after extraction and digestion of DNA. These preparation steps may cause spurious base oxidation, which is less likely to occur with methods such as the comet assay, which are based on nicking of the DNA strand at modified bases, but offer less specificity. The European Standards Committee on Oxidative DNA Damage has concluded that the true levels of the most widely studied lesion, 8-oxodG (8-oxo-7,8-dihydro-2'deoxyguanosine), in cellular DNA is between 0.5 and 5 lesions per 10(6) dG bases. Base excision repair of oxidative damage to DNA can be assessed by nicking assays based on oligonucleotides with lesions or the comet assay, by mRNA expression levels or, in the case of, e.g., OGG1 (8-oxoguanine DNA glycosylase 1), responsible for repair of 8-oxodG, by genotyping. Products of repair in DNA or the nucleotide pool, such as 8-oxodG, excreted into the urine can be assessed by MS-based methods and generally reflects the rate of damage. Experimental and population-based studies indicate that many environmental factors, including particulate air pollution, cause oxidative damage to DNA, whereas diets rich in fruit and vegetables or antioxidant supplements may reduce the levels and enhance repair. Urinary excretion of 8-oxodG, genotype and expression of OGG1 have been associated with risk of cancer in cohort settings, whereas altered levels of damage, repair or urinary excretion in case-control settings may be a consequence rather than the cause of the disease.