PMID- 18470304 OWN - NLM STAT- MEDLINE DCOM- 20080925 LR - 20230411 IS - 0091-6765 (Print) IS - 1552-9924 (Electronic) IS - 0091-6765 (Linking) VI - 116 IP - 5 DP - 2008 May TI - The polybrominated diphenyl ether mixture DE-71 is mildly estrogenic. PG - 605-11 LID - 10.1289/ehp.10643 [doi] AB - 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. 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-alpha. FAU - Mercado-Feliciano, Minerva AU - Mercado-Feliciano M AD - Department of Pharmacology and Toxicology, University School of Medicine, 975 W. Walnut St. (IB360), Indianapolis, IN 46202-5121 USA. FAU - Bigsby, Robert M AU - Bigsby RM LA - eng GR - F31 ES013341/ES/NIEHS NIH HHS/United States GR - R21 ES014367/ES/NIEHS NIH HHS/United States GR - ES013341/ES/NIEHS NIH HHS/United States GR - ES014367/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Environ Health Perspect JT - Environmental health perspectives JID - 0330411 RN - 0 (Endocrine Disruptors) RN - 0 (Estrogen Receptor Modulators) RN - 0 (Halogenated Diphenyl Ethers) RN - 0 (Phenyl Ethers) RN - 0 (Polybrominated Biphenyls) RN - 4TI98Z838E (Estradiol) RN - 7REL09ZX35 (pentabromodiphenyl ether) RN - 9035-51-2 (Cytochrome P-450 Enzyme System) SB - IM MH - Animals MH - Biological Assay MH - Breast Neoplasms/pathology MH - Cell Proliferation/drug effects MH - Cytochrome P-450 Enzyme System/analysis MH - Endocrine Disruptors MH - Estradiol/administration & dosage MH - Estrogen Receptor Modulators/*pharmacology MH - Female MH - Halogenated Diphenyl Ethers MH - Liver/cytology/drug effects MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Ovariectomy MH - Phenyl Ethers/administration & dosage/*pharmacology MH - Polybrominated Biphenyls/administration & dosage/*pharmacology PMC - PMC2367668 OTO - NOTNLM OT - CYP1A OT - CYP2B OT - DE-71 OT - MCF-7 OT - PBDEs OT - endocrine disruptors OT - estrogens OT - mice OT - ovariectomized OT - polybrominated diphenyl ethers EDAT- 2008/05/13 09:00 MHDA- 2008/09/26 09:00 PMCR- 2008/05/01 CRDT- 2008/05/13 09:00 PHST- 2007/07/07 00:00 [received] PHST- 2008/01/25 00:00 [accepted] PHST- 2008/05/13 09:00 [pubmed] PHST- 2008/09/26 09:00 [medline] PHST- 2008/05/13 09:00 [entrez] PHST- 2008/05/01 00:00 [pmc-release] AID - ehp0116-000605 [pii] AID - 10.1289/ehp.10643 [doi] PST - ppublish SO - Environ Health Perspect. 2008 May;116(5):605-11. doi: 10.1289/ehp.10643.