Chemical and biochemical characteristics of O-demethylation of chlorotrianisene in the rat

The effects of NADPH concentration and of two inhibitors of the microsomal mixed function oxidase system [2-diethylaminoethyl-2,2-diphenyl valerate hydrochloride (SKF 525-A) and metyrapone] on rat liver microsomal O-demethylation of the triphenylethylene estrogen chlorotrianisene (CTA) were studied. Comparative data were obtained using untreated and phenobarbital-pretreated rats of both sexes. In the presence of microsomes from males, O-demethylation was induced slightly by phenobarbital (PB), and it was inhibited substantially by SKF 525-A, particularly with uninduced microsomes. Metyrapone had little inhibitory effect. In the presence of microsomes from females, O-demethylation was neither induced by PB nor inhibited significantly by SKF 525-A or metyrapone. Incubation of CTA with male rat microsomes afforded, after purification, a mixture of monophenolic metabolites which consisted primarily of a 1:1 mixture of E- and Z-desmethylchlorotrianisene (DMCTA).