Comparative Study on the Effect of Trichloroethylene on the Expression of P450 Isoforms in Rat Lung and Liver

Takayuki Nakahama, Shigenori Sarutani, and Yoshio Inouye

School of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi 274-8510, Japan

Trichloroethylene (TCE) is a highly toxic compound which belongs to the class of volatile halogenated hydrocarbons, which are well-known pollutants of drinking water and the atmosphere. The effects of moderately toxic concentration of TCE on the levels of cytochrome P450 (CYP) isoforms and on their phenobarbital (PB) induction in rats were studied. Monooxygenase activities associated with individual CYP isoforms, i.e., CYP1A, 2B, 2E1 and 3A, were measured in microsomal fractions prepared from both lungs and livers of male and female Wistar rats (7-weeks old). Differences in constitutive levels of CYP isoforms were observed between liver and lung of mock-treated rat ; microsomal CYP2B activity was solely detected in lung while the activities of CYP1A, 2E1 and 3A, but not 2B were detected in liver. Among these, the pulmonary CYP2B and hepatic CYP2E1 activities were reduced by TCE-treatment. PB-treatment resulted in the detection of increased levels of hepatic CYP1A and 2E1 and of pulmonary CYP2B activities, and also the appearance of hepatic CYP2B activity. Coadministration of TCE was suppressive against the activities of CYP isoforms except for hepatic CYP2E1 in PB-treated rats. The lowered CYP2B activity in the presence of TCE was accompanied by the reduction in the amount of CYP2B apoprotein.