Comparative study on the mode of action of chlorinated ethylenes on the expression of rat CYP forms

Many environmental chemicals (xenobiotics), including polychlorinated ethylenes (CEs), are known to be meta-bolically intoxicated via the formation of hazardous intermediates (referred to as biological activation), while the expression of metabolic enzymes might be interfered with by xenobiotics at various stages in a system to minimize their adverse biological effects on the host animals. Three CEs, i.e., tetrachloroethylene (PCE), trichloroethylene (TCE) and 1,1-dichloroethylene (1,1-DCE), were comparatively studied for their effects on the in vivo expression of CYP forms, which are responsible for their metabolic activation, as well as organospecificities between the liver and lung. Furthermore, their effects on the expression of CYP forms were studied in the animals simultaneously admin-istered with phenobarbital (PB), known as an inducer of CYP2B. Individual CEs were administered intraperito-neally at 0.5 g/kg alone or simultaneously with PB (80 mg/kg/d) to 7-week-old male Wistar rats weighing about 200 g. The testosterone hydroxylase activities, CYP2B- and 2E1-mRNA, and CYP2B- and 2E1-proteins were mea-sured 24 hr after the treatment. Testosterone 2β-hydroxylase (2βTSH) and 16βTSH activities are attributable to the functions of CYP3A2, and CYP2B plus CYP3A2, respectively. The induction of hepatic CYP2B in the PB-treated animals might be masked by the suppressive effect of CYP3A2 in terms of the 16βTSH activity, while the pulmo-nary 16βTSH activity was confined to the function of CYP2B, which was insensitive to the inducing effect of PB. The inhibition of hepatic 16βTSH activity was observed exclusively in the presence of 1,1-DCE, especially in PB