Influence of vinyl chloride monomer on G1/S checkpoint and related protein expression in hepatocytes

Objective To explore the impact of vinyl chloride monomer(VCM) on G₁/S checkpoints in hepatocytes and its mechanisms.Methods Human normal liver cells(HL-7702) were exposed to gaseous VCM at concentrations of 0.8%,2.5%,7.5%,15%,and 30%(volume fraction) and normal air(control group) for 48 hours.The fraction of cell cycle of HL-7702 was detected with flow cytometry; the expression levels of relevant proteins were detected with Western blot.Results After exposed to VCM lower than 7.5% for 48 hours,the ratio of the cells at G₀/G₁ phase increased with the increment of VCM concentration,and the proportion of 7.5% VCM exposed cells at G₀/G₁ phase was significantly higher than that of the control cells(78.52±4.46% vs.73.35±1.56%,P<0.01); whereas the proportion S phase for the cells exposed to 2.5% VCM decreased significantly compared to that of the control cells(10.97±0.17% vs.12.85±0.02%,P<0.05).The expressions of cyclin dependent kinase 4(CDK4) and P16 protein increased significantly in the cells exposed to 7.5% VCM compared with the control cells(all P<0.05).Conclusion Low-dose VCM exposure could induce G₁ phase arrest in human hepatocytes and the effect may be mainly related to the decreased P16 expression and increased CDK4 expression.