XENOBIOTIC METABOLISM AND ENZYME-INDUCTION IN ISOLATED RAT INTESTINAL MICROSOMES

Abstract

Intestinal microsomes were isolated from rats pretreated with 3-methylcholanthrene (MC), phenobarbital (PB) and pregnenolone-16.alpha.-carbonitrile (PCN). The metabolism of benzo[a]pyrene (BP), 7-ethoxyresorufin, 7-ethoxycoumarin and biphenyl were examined. MC induces a 30-fold increase in BP metabolism. With control microsomes, BP metabolism is inhibited by metyrapone, SKF 525-A [2-(diethylamino)ethyl-2,2-diphenylvalerate hydrochloride], and antimycin A, but is stimulated 4.5-fold by rotenone. With microsomes from MC-treated rats, BP metabolism is inhibited by metyrapone, SKF 525-A, antimycin A and rotenone. MC pretreatment increases 7-ethoxyresorufin de-ethylase by almost 20-fold and ethoxycoumarin de-ethylase by almost 18-fold. PB pretreatment produces less than a 2-fold increase in both de-ethylases. PCN pretreatment inhibits 7-ethoxyresorufin and 7-ethoxycoumarin de-ethylases. In rats fasted for 2 days, neither de-ethylase could be detected in intestinal microsomes. Biphenyl 2- and 4-hydroxylase activities were induced less than 4-fold by MC or PB pretreatment.