Hydrogen peroxide causes greater oxidation in cellular RNA than in DNA
Hydrogen peroxide causes greater oxidation in cellular RNA than in DNA
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DOI：
10.1515/bc.2005.040
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发表时间：
2005-04-01
影响因子：
3.7
通讯作者：
Cotgreave, IA
中科院分区：
文献类型：
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作者：
Hofer, T;Badouard, C;Cotgreave, IA
用O-18标记的过氧化氢攻击人A549肺上皮细胞（[O-18]-H2 O2），平行提取总RNA和DNA，并分析O-18标记的8-氧代-7，8-二氢鸟苷（[O-18]-8-oxoGuo）和8-oxo-7，8-dihydro-2'-deoxyguanosine（[O-18]-8-oxodGuo）分别采用高效液相色谱-电喷雾串联质谱（HPLC-MS/MS）。[O-18]-H2 O2暴露导致[O-18]-8-oxoGuo和[O-18]-8-oxodGuo的剂量-反应形成，并且RNA中鸟嘌呤的O-18-标记比DNA中的O-18-标记常见14-25倍。氧化的核酸加合物的形成和随后去除的动力学也被监测长达24小时。A549在RNA和DNA中显示出缓慢的加合物周转率，RNA中[O-18]-8-oxodGuo的半衰期约为12.5 h，DNA中[O-18]-8-oxodGuo的半衰期约为20.7 h。
Human A549 lung epithelial cells were challenged with O-18-labeled hydrogen peroxide ([O-18]-H2O2), the total RNA and DNA extracted in parallel, and analyzed for O-18-labeled 8-oxo-7,8-dihydroguanosine ([O-18]-8-oxoGuo) and 8-oxo-7,8-dihydro-2'-deoxyguanosine ([O-18]-8-oxodGuo) respectively, using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-MS/MS). [O-18]-H2O2 exposure resulted in dose-response formation of both [O-18]-8-oxoGuo, and [O-18]-8-oxodGuo and O-18-labeling of guanine in RNA was 14-25 times more common than in DNA. Kinetics of formation and subsequent removal of oxidized nucleic acids adducts were also monitored up to 24 h. The A549 showed slow turnover rates of adducts in RNA and DNA giving half-lives of approximately 12.5 h for [O-18]-8-oxoGuo in RNA and 20.7 h for [O-18]-8-oxodGuo in DNA, respectively.