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.
Disulfiram (DS) was administered perorally once a day 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 o f 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.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000032:analysis*; D001579:Benzopyrene Hydroxylase / Q000032:analysis*; D001580:Benzopyrenes / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis*; D004221:Disulfiram / Q000633:toxicity*; D004050:Ditiocarb / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007413:Intestinal Mucosa / Q000201:enzymology; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008861:Microsomes / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains
D001580:Benzopyrenes; D003577:Cytochrome P-450 Enzyme System; D004050:Ditiocarb; D001579:Benzopyrene Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases; D004221:Disulfiram