8-Oxo-2'-deoxyguanosine as a biomarker of tobacco-smoking-induced oxidative stress.
8-Oxo-2'-deoxyguanosine as a biomarker of tobacco-smoking-induced oxidative stress.
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DOI：
10.1016/j.freeradbiomed.2012.04.006
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发表时间：
2012-08-01
影响因子：
7.4
通讯作者：
Blair, Ian A.
中科院分区：
文献类型：
--
作者：
Mesaros, Clementina;Arora, Jasbir S.;Wholer, Ashley;Vachani, Anil;Blair, Ian A.
关键词：
7，8-二氢-8-氧代-2‘-脱氧鸟苷(8-oxo-dguo)是一种有用的氧化应激生物标志物。然而，它的分析可能具有挑战性，因为8-oxo-dguo必须在dGuo存在的情况下定量，而不能人工转换为8-oxo-dguo。尿液是研究种群的理想生物流体，因为它可以非侵入性地获得，而且由于与水解DNA相比，尿液中存在的dGuo的数量相对较少，因此发生人为氧化的可能性较小。以[15N5]-8-oxo-dGuo为内标的稳定同位素稀释液相色谱/选择反应监测-质谱仪(LC-SRM/MS)为8-oxo-dGuo分析提供了最高的专属性。此外，通过添加[13C1015N5]-dGuo并在分析过程中监测其转化为[13C1015N5]-8-oxo-dguo来确定人工产物的形成。采用稳定同位素稀释LC-SRM/MS法对尿液中8-oxo-dguo浓度进行归一化处理，以反映尿流的个体差异。结果表明，吸烟者的尿8-oxo-dguo浓度显著高于非吸烟者(无论是单纯尿液浓度还是肌酐排泄量归一化后)。8-oxo-dGuo的平均水平为1.65 ng/m L，归一化肌酐水平为1.72μg/g肌酐。因此，尿8-oxo-dGuo的稳定同位素稀释法LC-SRM/MS分析是对尿异前列腺素(IsoP)分析的补充，用于评估吸烟所致的氧化应激。这种方法对于使用多不饱和脂肪酸的研究特别有用，在这种研究中，花生四烯酸前体的减少可能会混淆等磷脂蛋白的测量。
7,8-Dihydro-8-oxo-2′-deoxyguanosine (8-oxo-dGuo) is a useful biomarker of oxidative stress. However, its analysis can be challenging because 8-oxo-dGuo must be quantified in the presence of dGuo, without artifactual conversion to 8-oxo-dGuo. Urine is the ideal biological fluid for population studies, since it can be obtained non-invasively and it is less likely that artifactual oxidation of dGuo can occur because of the relatively low amounts that are present when compared with hydrolyzed DNA. Stable isotope dilution liquid chromatography/selected reaction monitoring-mass spectrometry (LC-SRM/MS) with [15N5]-8-oxo-dGuo as internal standard provided the highest possible specificity for 8-oxo-dGuo analysis. Furthermore, artifact formation was determined by addition of [13C1015N5]-dGuo and monitoring its conversion to [13C1015N5]-8-oxo-dGuo during the analytical procedure. 8-Oxo-dGuo concentrations were normalized for inter-individual differences in urine flow by analysis of creatinine using stable isotope dilution LC-SRM/MS. A significant increase in urinary 8-oxo-dGuo was observed in tobacco smokers when compared with non-smokers using either simple urinary concentrations or after normalization for creatinine excretion. The mean levels of 8-oxo-dGuo were 1.65 ng/mL and the levels normalized to creatinine were 1.72 μg/g creatinine. Therefore, stable isotope dilution LC-SRM/MS analysis of urinary 8-oxo-dGuo complements urinary isoprostane (isoP) analysis for assessing tobacco-smoking-induced oxidative stress. This method will be particularly useful for studies that employ polyunsaturated fatty acids, where reduction in arachidonic acid precursor could confound isoP measurements.
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