Changes in the microsomal mixed function oxidase system with long-term trichloroethylene administration.

Trichloroethylene (Tri) continues to be extensively used as an industrial solvent for fats and oils.1) As a xenobiotic metabolized by the microsomal mixed function oxidase system (MFOS) Tri is able to destroy, inhibit and induce microsomal enzymes. Costa et al.2) reported that incubation of hepatic microsomes with NADPH and trichloroethylene resulted in decreased levels of cytochrome P-450, but no alteration in the levels of NADPH-cytochrome c reductase or cytochrome b5. In vivo study, a single inhalation of Tri (10,000 ppm) for a few hours3) or a single intraperitoneal injection of Tri (1.0 ml/kg body weight)4) did not change the levels of cytochrome P-450 or NADPH-cytochrome c reductase in rats. However, Savolainen et al." reported that repeated inhalation of Tri (200 ppm) for several days increased hepatic cytochrome P-450. Pessayre et al.4) reported that repeated administration of Tri (1.0 ml/kg, i.p.) for 5 days decreased microsomal P-450 but increased NADPH-cytochrome c reductase activity. These studies suggest that MFOS is destroyed or induced by the dose and duration of Tri administration. These studies of the effect of Tri on microsomal enzymes, however, have been done over less than 5-6 days' duration. It is not clear how microsomal enzymes are altered when Tri is administered or inhaled for longer durations. In this communication, the authors report the effect of Tri administration for 15 weeks on cytochrome P-450, cytochrorne b5 levels and NADPHcytochrome c reductase activity. We also investigated changes in body weight and main organ weights.