Estrogen-like properties of brominated analogs of bisphenol A in the MCF-7 human breast cancer cell line.
Tetrabromobisphenol A (TeBBPA) is a four-meta-brominated variant of bisphenol A (BPA) and is one of the most commonly used brominated flame retardants worldwide. We compared the estrogenic potency of TeBBPA, BPA and the brominated analogs mono- (MBBPA), di- (DBBPA), and tribromobisphenol A (TrBBPA) in the estrogen-dependent human breast cancer cell line MCF-7. All of the compounds competed with 17beta-estradiol for binding to the estrogen receptor, although the affinity of the test chemicals to the estrogen receptor was much lower than that of 17beta-estradiol. TrBBPA and TeBBPA showed a considerably lower access to the estrogen receptors within intact MCF-7 cells incubated in 100% serum compared to incubation in serum-free medium, indicating a strong binding to serum proteins. BPA, MBBPA, and DBBPA showed only a slightly reduced access to the receptors. All of the test compounds induced proliferation in MCF-7 cells, the potential decreasing with increasing number of bromo-substitutions. TeBBPA did not induce maximal cell growth, indicating cytotoxic effects at high concentrations. BPA and the brominated analogs, except TeBBPA, induced progesterone receptor and pS2 to the same extent as 17beta-estradiol, although at much higher concentrations. Our studies demonstrate that compared to 17beta-estradiol, BPA and the brominated analogs have much lower estrogenic potencies for all of the endpoints tested, TeBBPA being the least estrogenic compound.
Samuelsen
M
M
National Institute of Public Health, Department of Environmental Medicine, Torshov, Oslo, Norway. mari.samuelsen@folkehelsa.no
Olsen
C
C
Holme
J A
JA
Meussen-Elholm
E
E
Bergmann
A
A
Hongslo
J K
JK
D001559:Benzhydryl Compounds; D001667:Binding, Competitive; D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects; D004785:Environmental Pollutants; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006801:Humans; D010636:Phenols / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D011075:Polybrominated Biphenyls / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D013329:Structure-Activity Relationship; D000071163:Trefoil Factor-1; D014316:Tritium; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004785:Environmental Pollutants; D004958:Estradiol; D004968:Estrogens, Non-Steroidal; D010636:Phenols; D011075:Polybrominated Biphenyls; D011506:Proteins; D011980:Receptors, Progesterone; D000071163:Trefoil Factor-1; D014316:Tritium; D025521:Tumor Suppressor Proteins; C051838:TFF1 protein, human; C020806:tetrabromobisphenol A; C006780:bisphenol A; D000098826:Bisphenol A Compounds