Abstract
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.
