摘要
采用超高效液相色谱-串联质谱法对两种非对映异构体(6S,8S)1,N^2-丙基-2′-脱氧鸟苷(ProdG)和(6R,8R)ProdG加合物进行鉴定与分析。通过色谱保留时间及质谱碎裂方式分析,证明乙醛与2′-脱氧鸟苷(dG)反应可形成ProdG加合物。体外实验表明,乙醛能够诱导脱氧核糖核苷酸(DNA)形成ProdG加合物,并且(6R,8R)ProdG的生成量大于(6S,8S)ProdG的生成量。细胞实验结果显示,乙醛暴露能显著提高人肺胚成纤维细胞(MRC5)基因组DNA中ProdG加合物的水平,且ProdG加合物的水平与乙醛的暴露浓度呈正相关。此外,100μmol/L的乙醛暴露使(6R,8R)ProdG的含量从(6.4±0.3)个/10~8个碱基增加到(127.2±2.7)个/10~8个碱基,上调程度大于(6S,8S)ProdG(从(6.5±0.3)个/10~8个碱基增加到(115.3±2.5)个/10~8个碱基)。该工作为乙醛暴露所引起的DNA加合物水平上升提供了实验依据。
Ultra performance liquid chromatography-tandem mass spectrometry （ UPLC-MS/MS）was used for the identification and analysis of the two diastereomers of adducts（（6S,8S） 1,N2-propano-2′-deoxyguanosine（ProdG）and（6R,8R）ProdG）. By contrasting the chromato-graphic retention time and mass spectrographic fragmentation patterns with ProdG standard ,it was proved that ProdG addcuts can be formed from the reaction of 2′-deoxyguanosine（ dG ） with acetaldehyde. Vitro experiments showed that ProdG adducts can be formed in double stranded deoxyribonucleic acid（ DNA）by the induction of acetaldehyde,and the formation of （6R,8R）ProdG was higher than that of（ 6S,8S）ProdG. In cell experiments,acetaldehyde exposure can significantly increase the levels of ProdG adducts in genomic DNA of human embryonic lung fibroblast MRC5 cells,and the enhancement of ProdG was positively correlated with the concentration of acetaldehyde. In addition,the up-regulation of（6R,8R）ProdG was from 6. 4±0. 3 to 127. 2±2. 7 adducts per 108 nucleotides,higher than that of（ 6S,8S）ProdG from 6. 5±0. 3 to 115. 3±2. 5 adducts per 10 8 nucleotides by acetaldehyde exposure at 100μmol/L. This work provides an experimental basis for the up-regulation of DNA adducts induced by acetaldehyde exposure.
出处
《色谱》
CAS
CSCD
北大核心
2016年第8期757-761,共5页
Chinese Journal of Chromatography
基金
国家自然科学基金项目(21125523)
国家环保部环保公益专项(201309045)~~
关键词
超高效液相色谱-串联质谱
1
N2-丙基-2′-脱氧鸟苷加合物
乙醛
诱导
ultra performance liquid chromatography-tandem mass spectrometry（ UPLC-MS/MS）
1,N2-propano-2′-deoxyguanosine（ ProdG）adducts
acetaldehyde
induction
