The effect of long term treatment with disulfiram on content of cytochrome P-450 and on benzo(a)pyrene monooxygenase activity in microsomes isolated from the rat small intestinal mucosa

Abstract

Disulfiram (DS) was administered perorally once daily to rats for 30 days to investigate the effects on cytochrome P-450 content and benzo(a)pyrene (BP) monooxygenase activity in microsomes isolated from the small intestinal mucosa. 50 mg or 100 mg DS/kg body weight caused a dose-related increase in BP monooxygenase activity, whereas the content of cytochrome P-450 was increased at the higher dose only. Similar absorption characteristics of cytochrome P-450 and turnover rates for BP on the basis of cytochrome P-450 was observed among the different microsomal preparations. The addition of DS or diethyldithiocarbamate (DDTC) to incubates of intestinal microsomes inhibited BP monooxygenase activity. Microsomes isolated from DS-treated rats were however less sensitive to in vitro inhibition by DS.