Dose dependent activation of rat small intestinal monooxygenase-activity towards benzo(a)pyrene and 7-ethoxycoumarin after oral pretreatment with cimetidine.

Arylhydrocarbon-hydroxylase and 7-ethoxycoumarin O-deethylase were stimulated in intestinal microsomes prepared two hours after administration of cimetidine (25 mg/kg, p.o.) to male Wistar rats. Moreover, the metabolite-pattern of benzo(a)pyrene was changed as compared to that in control (saline, 2 hr) animals. Cytochrome P-450 content was not affected. However, rats receiving higher doses of cimetidine (75 and 150 mg/kg) showed a dose dependent decrease in diolformation from benzo(a)pyrene. We were not able to achieve similar effects on monooxygenase activity by in vitro pretreatment of intestinal cells and/or microsomes. Observed interaction might implicate an effect of cimetidine on carcinogenic activity in small intestine of polycyclic aromatic hydrocarbons.