摘要：It was demonstrated that trans -stilbene was metabolically activated to the estrogenic compound by rat liver microsomes (Sugihara et al. , Toxicol. Appl. Pharmacol. , 167, 46—54 (2000)). In this study, determination of the isoforms of cytochrome P450 involved in the oxidation of the proestrogen, trans -stilbene, to its hydroxylated metabolites was examined. When trans -stilbene was incubated with rat liver microsomes in the presence of NADPH, estrogenic compounds, trans -4-hydroxystilbene and trans -4,4′-dihydroxystilbene were formed. Comparison of the oxidase activity among liver microsomes of untreated, 3-methylcholanthrene-treated, acetone-treated, clofibrate-treated, dexamethasone-treated and phenobarbital-treated rats toward trans -stilbene showed that those from 3-methylcholanthrene-treated rats exhibited the highest activity. Human liver microsomes also catalyzed the oxidation in varying degrees. Variation in trans -stilbene oxidase activity was closely correlated to that of phenacetin O -deethylase activity. The oxidase activity was inhibited by α-naphthoflavone; however, in this case trans -4,4′-dihydroxystilbene was not detected. The oxidase activity toward trans -stilbene was exhibited by recombinant human cytochrome P450 1A1 and 1A2 expressed in a human B lymphoblastoid cell line.
