Abstract:

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.

Key words: 1,N²-propano-2'-deoxyguanosine (ProdG) adducts, acetaldehyde, induction, ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)