Metabolic activation of the proestrogens trans-stilbene and trans-stilbene oxide by rat liver microsomes.
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| Abstract |
A liver microsome-mediated activation of the proestrogens trans-stilbene and trans-stilbene oxide was found in this study. trans-Stilbene and trans-stilbene oxide were negative in estrogen reporter assay using estrogen-responsive human breast cancer cell line MCF-7 and growth assay in rat pituitary tumor cell line MtT/E-2. However, these compounds exhibited estrogenic activity after incubation with liver microsomes of 3-methylcholanthrene-treated rats in the presence of NADPH. In contrast, cis-stilbene and cis-stilbene oxide did not show estrogenic activity after such incubation. When trans-stilbene was incubated with the liver microsomes of 3-methylcholanthrene-treated rats in the presence of NADPH, two metabolites were detected by HPLC. They were identified unequivocally as trans-4-hydroxystilbene and trans-4, 4'-dihydroxystilbene by mass and UV spectral comparison with authentic samples. The oxidase activity of the liver microsomes toward trans-stilbene was inhibited by SKF 525-A and alpha -naphthoflavone. Minor activity was observed when liver microsomes of untreated or phenobarbital-treated rats were used instead of those from 3-methylcholanthrene-treated rats. trans-4-Hydroxystilbene and trans-4,4'-dihydroxystilbene exhibited significant estrogenic activities. These results suggest that the estrogenic activities of trans-stilbene and trans-stilbene oxide were due to formation of hydroxylated metabolites.
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| Authors | K Sugihara, S Kitamura, S Sanoh, S Ohta, N Fujimoto, S Maruyama, A Ito |
| Journal | Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 167 Issue 1 Pg. 46-54 (Aug 15 2000) ISSN: 0041-008X [Print] United States |
| PMID | 10936078 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright 2000 Academic Press. |
| Chemical References |
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