Comparison of the reporter gene assay for ER-alpha antagonists with the immature rat uterotrophic assay of 10 chemicals.
We performed a reporter gene assay for estrogen receptor (ER)-alpha agonists and antagonists of 10 chemicals that showed both estrogen agonistic and reduced the estrogenic effect of ethinyl estradiol in a rat uterotrophic assay. The chemicals tested by the immature uterotrophic assay were p-(tert-pentyl)phenol, 4,4'-thiobis-phenol, 4,4'-(hexafluoroisopropylidene)diphenol, 2,2-bis(4-hydroxyphenyl)-4-methyl-n-pentane, 4,4'-(octahydro-4,7-methano-5H-inden-5-ylidene)bisphenol, 4-(phenylmethyl)phenol, 4,4'-dihydroxybenzophenone, 2,2',4,4'-tetrahydroxybenzophenone, 4-hydroxybenzophenone and 2,4,4'-trihydroxybenzophenone. Although all chemicals examined in this study were positive in the reporter gene assay for ER-alpha agonists, 4,4'-(octahydro-4,7-methano-5H-inden-5-ylidene)bisphenol was only positive in the reporter gene assay for ER-alpha antagonists. These findings demonstrate that results of the reporter gene assay for ER-alpha agonists correlated well with those of the uterotrophic assay, but antagonistic change of 9 of 10 chemicals in the uterotrophic assay was not detected by the reporter gene assay for ER-alpha antagonists.
Yamasaki
Kanji
K
Chemicals Assessment Center, Chemicals Evaluation and Research Institute, 3-822, Ishii, Hita, Oita 087-0061, Japan. yamasaki-kanji@ceri.or.jp
Takeyoshi
Masahiro
M
Yakabe
Yoshikuni
Y
Sawaki
Masakuni
M
Takatsuki
Mineo
M
D000818:Animals; D001577:Benzophenones / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D004997:Ethinyl Estradiol / Q000494:pharmacology; D005260:Female; D017930:Genes, Reporter / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics; D010636:Phenols / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000819:agonists* / Q000037:antagonists & inhibitors*; D013629:Tamoxifen / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects*
D001577:Benzophenones; D047628:Estrogen Receptor alpha; D010636:Phenols; D011960:Receptors, Estrogen; D013629:Tamoxifen; D004997:Ethinyl Estradiol; D008156:Luciferases