The Polybrominated diphenyl ether mixture DE-71 ls. Mildly estrogenic

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 PRIDE 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.