超高效液相色谱-串联质谱法鉴定与分析乙醛诱导脱氧核糖核苷酸加合物

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，N²-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，100 μ mol/L的乙醛暴露使（6R，8R）ProdG的含量从（6.4±0.3） 个/10⁸个碱基增加到（127.2±2.7） 个/10⁸个碱基，上调程度大于（6S，8S）ProdG（从（6.5±0.3） 个/10⁸个碱基增加到（115.3±2.5） 个/10⁸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。

Identification and analysis of acetaldehyde induced deoxyribonucleic acid adducts by ultra performance liquid chromatography-tandem mass spectrometry

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 chromatographic 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 10⁸ nucleotides by acetaldehyde exposure at 100 μ mol/L. This work provides an experimental basis for the up-regulation of DNA adducts induced by acetaldehyde exposure.