Hepatic drug metabolizing enzymes induced by clofibrate in rasH2 mice

Hepatic drug metabolizing enzyme activities were determined, after treatmen t with clofibrate, in transgenic mice carrying human c-Ha-ras (rasH2 mice). Changes in the drug metabolizing enzyme activities in these mice by gene i ntegration were also evaluated. Male and female rasH2 mice (Tg) and the lit ter mates not carrying the gene (non-Tg) received orally 500 mg/kg of clofi brate or the vehicle for 12 consecutive days. Liver homogenate and microsom es were prepared and the contents and activities of cytochrome P450 (CYP), cytochrome b5 content and enzyme activities related to peroxisome prolifera tion were determined. Relative liver weights, CYP4A and activities of catal ase and carnitine palmitoyl transferase increased to the same extent in Tg and non-Tg mice treated with clofibrate. In Tg and non-Tg groups that recei ved vehicle, contents and activities of CYP and cytchrome b5 contents were comparable. It was concluded that gene integration did not alter drug metab olizing enzymes and responses to clofibrate. (C) 2000 Elsevier Science Irel and Ltd. All rights reserved.