| The Polybrominated Diphenyl Ether Mixture DE-71 Is Mildly Estrogenic Minerva Mercado-Feliciano1 and Robert M. Bigsby2 1Department of Pharmacology and Toxicology, and 2Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana, USA Abstract
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-α 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. Conclusion: 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-α. Key words: CYP1A, CYP2B, DE-71, endocrine disruptors, estrogens, MCF-7, mice, ovariectomized, PBDEs, polybrominated diphenyl ethers. Environ Health Perspect 116:605–611 (2008) . doi:10.1289/ehp.10643 available via http://dx.doi.org/ [Online 29 January 2008]
Address correspondence to R.M. Bigsby, Department of Obstetrics and Gynecology, Indiana University School of Medicine, 975 W. Walnut St. (IB360) , Indianapolis, IN 46202-5121 USA. Telephone: (317) 274-8970. Fax: (317) 278-2884. E-mail: rbigsby@iupui.edu We thank G. Eckert for assistance with the statistical analyses. This work was supported by grants ES013341 and ES014367 from the National Institute of Environmental Health Sciences. The authors declare they have no competing financial interests. Received 7 July 2007 ; accepted 25 January 2008.
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