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J.Health Sci., 49(2), 91-98, 2003
Estrogenicity of Metabolites of Benzophenone Derivatives Examined by a Yeast Two-Hybrid
Assay
Satoshi Takatori,*, a Yoko
Kitagawa,a Hajime
Oda,a Gunpei
Miwa,b Jun-ichi
Nishikawa,b Tsutomu
Nishihara,b Hiroyuki
Nakazawa,c and Shinjiro
Horia
aOsaka Prefectural Institute of Public Health, 3-69, 1-chome, Nakamichi, Higashinari-ku, Osaka 537-0025, Japan,
bGraduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-087, Japan, and
cFaculty of Pharmaceutical Sciences, Hoshi University, 4-41, 2-chome, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
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 37°C 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.
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