Induction of hepatic microsomal mixed function oxidase system by ethylenethiourea in mice

Oral administration to mice of ethylenethiourea (ETU) at single doses from 50 to 600 mg/kg caused a dose-dependent increase (up to 200 mg/kg) in hepatic microsomal aniline hydroxylase (AH) without affecting aminopyrine-N-demethylase activity or total microsomal cytochrome P-450 content. Maximal (2.4 fold) enzyme increase was observed 24 h after treatment by an ETU dose of 200 mg/kg and was followed by a return to control levels within 4 days. Pretreatment of mice with actinomycin D completely prevented the increase of AH, while the addition in vitro to the incubation mixture of ETU at concentrations up to 1 mM did not cause any changes of enzymatic activity. These data speak in favour of an induction of AH via de novo protein biosynthesis. A more detailed analysis of the phenomenon indicated that the stimulatory effect of ETU on AH did not add to that produced by beta-naphthoflavone, but added to that due to phenobarbital. Therefore ETU and beta-naphthoflavone appear to affect similar mechanisms inducing aniline hydroxylase activity.