Department of Toxicology, School of Public Health, 74648Shanxi Medical University, Taiyuan, China.
Department of Statistics, School of Public Health, 74648Shanxi Medical University, Taiyuan, China.
Toxicol Ind Health. 2022 Jul;38(7):377-388. doi: 10.1177/07482337221098600. Epub 2022 May 12.
To explore the epigenetic mechanism of deoxyribonucleic acid (DNA) damage induced by vinyl chloride (VC), we studied the micronuclei of peripheral blood lymphocytes in 193 subjects (92 in a VC exposure group employed in a chlorine-alkali plant; 101 in a control group employed in a power plant) and selected three pairs from the subjects (exposed and control) for whole-genome bisulfite sequencing (WGBS). The results showed that the rate of micronucleus formation in the VC exposure group was higher than that of control group (6.05 ± 3.28‰ vs. 2.01 ± 1.79‰). A total of 9534 differentially methylated regions (DMRs) were identified by WGBS, of which 4816 were hypomethylated and 4718 were hypermethylated. The Kyoto encyclopedia of genes and genomes (KEGG) pathway and gene ontology (GO) analyses showed the top three KEGG pathways were cancer , neuroactive ligand-receptor interaction, and axon guidance, and the top three GO-BP pathways enriched were multicellular organismal process, developmental process, and anatomical structure development. In the most enriched DMR pathway (pathways in cancer), we found that , , , , and were hypermethylated, and the methylation levels of and were decreased. The methylation of differentially methylated genes (DMGs) mentioned above were verified by methylation-specific PCR (MSP) and agarose gel electrophoresis (AGE) in 50 pairs of subjects, where the coincidence rate was 60-100%. In conclusion, the epigenetic perturbations of specific DMGs (, , , , , , and ) may be associated with DNA damage from vinyl chloride exposure.
为了探索氯乙烯（VC）导致脱氧核糖核酸（DNA）损伤的表观遗传机制，我们研究了 193 名受试者（氯碱厂接触 VC 的 92 名，电厂对照的 101 名）外周血淋巴细胞的微核，从这些受试者中选择了三对（暴露组和对照组）进行全基因组亚硫酸氢盐测序（WGBS）。结果显示，VC 暴露组微核形成率高于对照组（6.05±3.28‰比 2.01±1.79‰）。WGBS 共鉴定出 9534 个差异甲基化区域（DMR），其中 4816 个呈低甲基化，4718 个呈高甲基化。京都基因与基因组百科全书（KEGG）通路和基因本体论（GO）分析显示，前三个 KEGG 通路为癌症、神经活性配体-受体相互作用和轴突导向，前三个 GO-BP 通路富集为多细胞生物过程、发育过程和解剖结构发育。在最富集的 DMR 通路（癌症通路）中，我们发现、、、、和呈高甲基化，和的甲基化水平降低。上述差异甲基化基因（DMGs）的甲基化通过 50 对受试者的甲基化特异性 PCR（MSP）和琼脂糖凝胶电泳（AGE）进行了验证，其符合率为 60-100%。综上所述，特定 DMGs（、、、、、、和）的表观遗传扰动可能与氯乙烯暴露引起的 DNA 损伤有关。
