Role of CYP1A2 gene in trichlorethylene toxicity

Objective To study the role of CYP1A2 gene in trichlorethylene (TCE) toxicity by molecular cloning technology. Methods CYP1A2-silenced hepatocytes and hepatocytes with CYP1A2 gene over expression have been previously constructed by our laboratory. The normal hepatocytes(L02 cells),CYP1A2-silenced hepatocytes and hepatocytes with CYP1A2 gene over expression were treated with TCE for 12 h at doses of 0.25, 0.50, 1.00, 2.00 and 4.00 mmol/L,then the expression of apoptosis genes(Bcl-2、Caspase-3、Caspase-8、Caspase-9) and oncogenes(c-fos、c-myc、k-ras、P53) was observed. Results After TCE treatment,Bcl-2 expression levels in CYP1A2-silenced hepatocytes increased when compared with that of control(P<0.01),while the mRNA expression levels of apoptosis genes(Caspase-3,Caspase-8,Caspase-9) and oncogenes (c-fos,c-myc) decreased in CYP1A2-silenced hepatocytes compared with that in control(P<0.05 or P<0.01). Additionally,Bcl-2 levels were significantly lower in CYP1A2-overexpressed hepatocytes than that of control(P<0.01),the expression levels of apoptosis genes(Caspase-3,Caspase-8,Caspase-9) and oncogenes(c-fos,c-myc,k-ras) increased significantly in CYP1A2-overexpressed hepatocytes when compared with the control,but P53 levels were significantly lower than that of the control (P<0.01). Conclusion These findings indicated that CYP1A2 plays an important role in TCE metabolism in vivo. CYP1A2 gene silencing could reduce TCE activation in hepatocytes,subsequently lead to decrease of apoptosis genes and oncogenes expression treatment. However,CYP1A2 gene over expression seems to promote apoptosis genes and oncogenes expression after TCE treatment.