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.
Meneguz
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Michalek
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D000815:Aniline Hydroxylase / Q000096:biosynthesis; D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005031:Ethylenethiourea / Q000633:toxicity*; D007093:Imidazoles / Q000633:toxicity*; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D010634:Phenobarbital / Q000494:pharmacology; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D007093:Imidazoles; D003609:Dactinomycin; D005031:Ethylenethiourea; D019324:beta-Naphthoflavone; D006899:Mixed Function Oxygenases; D000815:Aniline Hydroxylase; D010634:Phenobarbital