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Toxic effect of trichloroethylene on liver cells with CYP3A4 gene defect
Author(s): 
Pages: 421-425
Year: Issue:  6
Journal: Chinese Journal of Industrial Hygiene and Occupational Diseases

Keyword:  Normal human liver cellTrichloroethyleneApoptosis geneOncogenes;
Abstract: Objective To investigate the toxic effect of trichloroethylene on liver cells with CYP3A4 gene defect.Methods The normal human liver cells (L02 cells) and liver cells with CYP3A4 gene defect were exposed to trichloroethylene at different doses (0.0,0.4,0.8,1.6,3.2,and 6.4 mmol/L).CCK8 assay and RT-qPCR were used to measure cell viability and changes in the expression of apoptosis genes and oncogenes.Results After being exposed to trichloroethylene at doses of 1.6,3.2,and 6.4 mmol/L,the liver cells with CYP3A 4 gene defect showed significantly higher cell viability than L02 cells (0.91±0.06/0.89±0.05/0.85±0.07 vs 0.80±0.04/0.73 ±0.06/0.67 ±0.07,P<0.05).The L02 cells in the 0.8 ~3.2 mmol/L trichloroethylene groups showed significant increases in the expression of the apoptosis genes caspase-3,caspase-8,and caspase-9 (P<0.05),as well as the oncogenes c-myc,c-fos,and k-ras (P<0.05).Compared with the L02 cells,the cells with CYP3A4 gene defect showed significant reductions in the expression of the apoptosis genes caspase-3,caspase-8,and caspase-9 and the oncogenes c-myc,c-fos,and k-ras (P<0.05).Conclusion Trichloroethylene exposure has a less effect on the expression of apoptosis genes and oncogenes in liver cells with CYP3A4 gene defect than in normal human liver cells,suggesting that CYP3A4 gene defect reduces the inductive effect of trichloroethylene on apoptosis genes and oncogenes.
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