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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 BCL2 , TJP2 , TAOK1 , PFKFB3 , LIPI, and LIPH were hypermethylated, and the methylation levels of BNIP1 and GRPEL2 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 ( BCL2 , TJP2 , TAOK1 , PFKFB3 , LIPI , LIPH , BNIP1, and GRPEL2 ) may be associated with DNA damage from vinyl chloride exposure.

Vinyl chloride (VC) is a confirmed human carcinogen associated with hepatocellular carcinoma and angiosarcoma. However, the role of microRNAs (miRNAs) in liver cell cycle changes under VC exposure remains unclear, which prevents research on the mechanism of VC-induced carcinogenesis. In this study, male rats were injected intraperitoneally with VC (0, 5, 25, and 125 mg/kg body weight) for 6, 8, and 12 weeks. Cell cycle analysis of liver cells, miRNA-222, miRNA-199a, miRNA-195, and miRNA-125b expression in the liver and serum, and target protein expression were performed at different time points. The results showed a higher percentage of hepatocytes in the G1/G0 and S phases at the end of 6 and 12 weeks of VC exposure, respectively. MiRNA-222 expression decreased initially and then increased, whereas miRNA-199a, miRNA-195, and miRNA-125b expression increased initially and then decreased, which corresponded with changes in cell cycle distribution and related target proteins expression (p27, cyclinA, cyclinD1, and CDK6). The corresponding expression levels of miRNAs in serum did not change. Dynamic changes in miR-222, miR-199a, miR-195, and miR-125b induced by VC can lead to cell cycle deregulation by affecting cell cycle-related proteins, and these miRNAs can serve as early biomarkers for malignant transformation caused by VC.

Objective: To explore the relationship between genetic polymorphism of APE1, XRCC1 and susceptibility of chromosomal damage induced by vinyl chloride monomer (VCM)., Methods: 75 workers occupationally exposed to VCM were investigated. Chromosome damage in peripheral lymphocyte were measured by cytokinesis-block micronucleus (CB-MN) test. Created restriction site-restrained fragment length polymorphism (CRS-RFLP) and PCR-RFLP technique was applied to detect single nucleotide polymorphisms (SNPs) in APE1 gene (c.148) and XRCC1 gene (c. 194, c.280 and c. 399)., Results: The frequencies of the Asp and Glu alleles of APE1 148 in our study population were 61% and 39%, respectively. The frequencies of occurrence of the Arg and Trp alleles of XRCC1 194 were 85% and 15%. The frequencies of occurrence of the Arg and His alleles of XRCC1 280 were 85% and 15%, too. Whereas the prevalence of Arg allele was 87.0% and XRCC1 399 allele Gln was 13.0%. The risk of chromosomal damage induced by VCM for individuals carrying XRCC1 c. 194 Arg/Arg genotype was 0.6898 (95% CI 0.4997 - 0.9333, P = 0.0195) of those carrying Arg/Trp, Trp/Trp genotypes. The risk of chromosomal damage for female VCM exposure workers was 1.6000 (95% CI 1.2284 - 2.0699, P = 0.0004) of male workers. The haplotypes TGG/CGG and TGG/CAGCGGG were associated with the decreased frequencies of total micronucleus ( P < 0. 05)., Conclusion: It was suggested that female workers and subjects carrying XRCC1 194 Arg/Arg genotypes could be higher risk of chromosomal damage when they exposed to VCM.