URINARY 8-HYDROXY-2'-DEOXYGUANOSINE AS A BIOLOGICAL MARKER OF INVIVO OXIDATIVE DNA DAMAGE
URINARY 8-HYDROXY-2'-DEOXYGUANOSINE AS A BIOLOGICAL MARKER OF INVIVO OXIDATIVE DNA DAMAGE
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DOI：
10.1073/pnas.86.24.9697
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发表时间：
1989-12-01
影响因子：
11.1
通讯作者：
AMES, BN
中科院分区：
文献类型：
--
作者：
SHIGENAGA, MK;GIMENO, CJ;AMES, BN
DNA受到内源性氧化剂的持续氧化损伤。氧化的DNA不断被修复，氧化的碱基随尿液排出体外。描述了一种简单的常规分析方法，用于尿8-羟基-2”-脱氧鸟苷，一种氧化DNA损伤加合物，作为人类和啮齿动物氧化损伤的指标。该加合物从人尿中纯化并进行了表征。所描述的分析采用一系列固相萃取步骤，将8-羟基-2”-脱氧鸟苷从其他尿液成分中分离出来，然后通过梯度反相高效液相色谱耦合到双电极高效电化学检测系统进行分析。用这种方法对三个物种的尿液进行分析表明，小鼠排泄的8-羟基-2”-脱氧鸟苷大约是人类的3.3倍（每个细胞每天582个残留物对178个残留物），这一结果支持了DNA氧化损伤与物种特异性基础代谢率成比例增加的建议。
DNA is subject to constant oxidative damage from endogenous oxidants. The oxidized DNA is continuously repaired and the oxidized bases are excreted in the urine. A simple routine analytical procedure is described for urinary 8-hydroxy-2''-deoxyguanosine, an oxidative DNA damage adduct, as an indicator of oxidative damage in human and rodents. This adduct was purified from human urine and characterized. The described assay employs a series of solid-phase extraction steps that separate 8-hydroxy-2''-deoxyguanosine from other urinary constituents, followed by analysis by gradient reversed-phase HPLC coupled to a dual-electrode high-efficiency electrochemical detection system. Analysis of urine from three species by this method indicates that mice excrete approximately 3.3-fold more 8-hdyroxy-2''-deoxyguanosine than humans (582 vs. 178 residues per cell per day), a result that supports the proposal that oxidative damage to DNA increases in proportion to species-specific basal metabolic rates.