Objective: To compare the trichloroethylene (TCE) -induced alteration in cell proliferation, cell apoptosis, histone deacetylase activity and expression levels in human hepatic L-02 cells (L-02 cells) and SET deficient cells, and reveal the TCE-induced effect in histone modification and the role of SET on epigenetic pathway.
Methods: The L-02 cells and preestablished SET deficient cells were treated with different TCE concentrations. For the changes of cell proliferation level and apoptosis rate, The L-02 cells and SET deficiency cells without TCE treatment were served as the control group, the TCE treatment was in the concentration of 2.0 and 8.0 mmol/L for 24 h. For histone deacetylase activity and expression levels, the TCE treatment was in the concentration of 0.25, 0.50, 1.0, 2.0, 4.0, and 8.0 mmol/L for 24 h.
Results: After treatment with TCE for 24 h, the cell proliferation level was significantly decreased and the apoptotic rate was significantly increased in both cell lines. When concentration of TCE were reached to 8.0 mmol/L, the difference of cell proliferation level and apoptotic rate between two groups was statistically significant (t=-4.362 for proliferation level and t=23.950 for apoptotic rate, both P<0.05). After treatment with TCE for 24 h in various concentration (0, 0.25, 0.50, 1.00, 2.00, 4.00 and 8.00 mmol/L) , the activity of histone deacetylases was significantly increased in both cell lines. When the TCE concentration were high than 0.50 mmol/L, compared with control group of L-02 cells, the enzymes activity were significantly increased (F=403.26, P<0.001). When TCE concentration was reached 1.00 mmol/L, the enzyme activity is highest. Compared with control group of SET deficiency cells, the enzyme activity was significantly increased when TCE concentration was reached 1.00 mmol/L (F=44.01, P<0.001). When concentration of TCE reached 0.50 mmol/L, the difference of enzyme activity between two groups was statistically significant. For the protein expression, compared with control group of L-02 cells, TCE exposure can induced a significant increased expression level of HDAC2 in TCE-treated L-02 cells (F values were 79.99, P<0.001). But the alteration in SET deficiency cells was not significant.
Conclusion: TCE exposure can induce a significant alteration on cell proliferation, apoptotic rate and, the activity and expression on histone deacetylases. SET deficiency can attenuate the TCE-induced alteration in histone modification in L-02 cells. Our results indicated that SET is involved in the mechanism of TCE-induced cytotoxicity and epigenetic regulation in L-02 cells.