Estrogenicity of metabolites of benzophenone derivatives examined by a yeast two-hybrid assay

The estrogenic activities of S-9 metabolites of benzophenone derivatives (benzophenone, 2-hydroxy-4-methoxybenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone, 2-hydroxy-4-octyloxybenzophenone, 2,4-dihydroxybenzophenone and 2,3,4-trihydroxybenzophenone) and benzhydrol were examined with a yeast two-hybrid screening system. After chemicals were incubated in an S-9 mix at 37degreesC for 4 hr prior to their incubation with the yeast strain, the S-9 mix containing metabolites was assayed for the estrogenic activity by the yeast two-hybrid assay. Benzophenone, 2-hydroxy-4-methoxybenzophenone and 2,2'-dihydroxy-4-methoxybenzophenone exhibited estrogenic activities after incubation with the S-9 mix. The estrogenic metabolites of 2-hydroxy-4-methoxybenzophenone were fractionated by high-performance liquid chromatography, one of which was identified as 2,4-dihydroxybenzophenone. This assay will be a useful tool for detecting proestrogens.