The polybrominated diphenyl ether mixture DE-71 is mildly estrogenic.
BACKGROUND
Polybrominated diphenyl ethers (PBDEs) are widely found in the environment, and they may act as endocrine disruptors.


OBJECTIVE
Our goal in this study was to test the PBDE mixture DE-71 for estrogenic activity.


METHODS
We used proliferation of cultured breast cancer cells (MCF-7) and trophic effects in the reproductive tracts of ovariectomized mice as estrogen bioassays. DE-71 was administered to mice by subcutaneous injection (sc) or oral gavage (po), alone or in combination with estradiol, for 3 or 34 days. Liver weights and cytochrome P450 enzyme activities were also measured.


RESULTS
DE-71 increased MCF-7 cell proliferation, and this was prevented by antiestrogen. DE-71 cotreatment reduced the effect of estradiol in MCF-7 cells. In the mouse 3-day assay, DE-71 administered alone had no effect on uterine weight, uterine epithelial height (UEH), or vaginal epithelial thickness (VET); however, when DE-71 was administered as a cotreatment, it potentiated estradiol's effect on uterine weight. DE-71 administered sc to BALB/c mice for 34 days slightly increased UEH and VET, and attenuated the estradiol-induced increase in UEH; these effects were not seen in BALB/c mice treated po or in C57BL/6 mice treated sc. DE-71 increased liver weight in BALB/c, C57BL/6, and estrogen receptor-alpha knockout mice. We also found an increase in liver cytochrome P450 1A (CYP1A) and CYP2B activities when DE-71 was administered po, but only CYP2B increased after sc treatment.


CONCLUSIONS
DE-71 behaves as a weak estrogen. In mice, the treatment route and duration determined if DE-71 was estrogenic. BALB/c mice are more susceptible to DE-71 effects in estrogen target tissues than C57BL/6 mice. DE-71 increased liver weight independently of estrogen receptor-alpha.
Mercado-Feliciano
Minerva
M
Department of Pharmacology and Toxicology, University School of Medicine, 975 W. Walnut St. (IB360), Indianapolis, IN 46202-5121 USA.
Bigsby
Robert M
RM
D000818:Animals; D001681:Biological Assay; D001943:Breast Neoplasms / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D052244:Endocrine Disruptors; D004958:Estradiol / Q000008:administration & dosage; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D005260:Female; D055768:Halogenated Diphenyl Ethers; D008099:Liver / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010052:Ovariectomy; D010647:Phenyl Ethers / Q000008:administration & dosage / Q000494:pharmacology*; D011075:Polybrominated Biphenyls / Q000008:administration & dosage / Q000494:pharmacology*
D052244:Endocrine Disruptors; D020847:Estrogen Receptor Modulators; D055768:Halogenated Diphenyl Ethers; D010647:Phenyl Ethers; D011075:Polybrominated Biphenyls; D004958:Estradiol; C086401:pentabromodiphenyl ether; D003577:Cytochrome P-450 Enzyme System