Skip to main content
Log in

Estrogen-like properties of brominated analogs of bisphenol A in the MCF-7 human breast cancer cell line

  • Published:
Cell Biology and Toxicology Aims and scope Submit manuscript

Abstract

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 17β-estradiol for binding to the estrogen receptor, although the affinity of the test chemicals to the estrogen receptor was much lower than that of 17β-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 17β-estradiol, although at much higher concentrations. Our studies demonstrate that compared to 17β-estradiol, BPA and the brominated analogs have much lower estrogenic potencies for all of the endpoints tested, TeBBPA being the least estrogenic compound.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Andersen HR, Andersson AM, Arnold SF, et al. Comparison of short-term estrogenicity tests for identification of hormone-disrupting chemicals. Environ Health Perspect. 1999; 107(supplement 1):89–108.

    PubMed  CAS  Google Scholar 

  • Ashby J., Tinwell H, Haseman J. Lack of effects for low dose levels of bisphenol A and diethylstilbestrol on the prostate gland of CF1 mice exposed in utero. Regul Toxicol Pharmacol. 1999; 30(2 Pt 1):156–66.

    Article  PubMed  CAS  Google Scholar 

  • Asplund L, Athanasiadou M, Sjödin A, Bergman Å, Börjeson H. Organohalogen substances in muscle, egg and blood from healthy Baltic salmon (salmo salar) and Baltic salmon that produced offspring with the M74 syndrome. Ambio. 1999;28:67–76.

    Google Scholar 

  • Bolger R, Wiese TE, Ervin K, Nestich S, Checovich W. Rapid screening of environmental chemicals for estrogen receptor binding capacity. Environ Health Perspect. 1998;106(9):551–7.

    PubMed  CAS  Google Scholar 

  • Brotons JA, Olea-Serrano MF, Villalobos M, Pedraza V, Olea N. Xenoestrogens released from lacquer coatings in food cans. Environ Health Perspect. 1995;103(6):608–12.

    PubMed  CAS  Google Scholar 

  • Brunborg G, Holme JA, Soderlund EJ, Omichinski JG, Dybing E. An automated alkaline elution system: DNA damage induced by 1,2-dibromo-3-chloropropane in vivo and in vitro. Anal Biochem. 1988;174(2):522–6.

    Article  PubMed  CAS  Google Scholar 

  • Colborn T, vom SF, Soto AM. Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environ Health Perspect. 1993;101(5):378–84.

    PubMed  CAS  Google Scholar 

  • Daston GP, Gooch JW, Breslin WJ, et al. Envíronmental estrogens and reproductive health: a discussion of the human and environmental data. Reprod Toxicol. 1997;11(4):465–81.

    Article  PubMed  CAS  Google Scholar 

  • Engeland A, Haldorsen T, Tretli S, et al. Prediction of cancer incidence in the Nordic countries up to the years 2000 and 2010. A collaborative study of the five Nordic Cancer Registries. APMIS Suppl. 1993;38:1–124.

    PubMed  CAS  Google Scholar 

  • Feldman D, Krishnan A. Estrogens in unexpected places: possible implications for researchers and consumers. Environ Health Perspect. 1995;103:129–33.

    PubMed  CAS  Google Scholar 

  • Fry DM, Toone CK. DDT-induced feminization of gull embryos. Science. 1981;213(4510):922–4.

    PubMed  CAS  Google Scholar 

  • Gaido KW, Leonard LS, Lovell S, et al. Evaluation of chemicals with endocrine modulating activity in a yeast-based steroid hormone receptor gene transcription assay. Toxicol Appl Pharmacol. 1997;143(1):205–12.

    Article  PubMed  CAS  Google Scholar 

  • Guillette LJJ, Gross TS, Masson GR, Matter JM, Percival HF, Woodward AR. Developmental abnormalities of the gonad and abnormal sex hormone concentrations in juvenile alligators from contaminated and control lakes in Florida. Environ Health Perspect. 1994;102(8):680–8.

    PubMed  CAS  Google Scholar 

  • Inouye B, Katayama Y, Ishida T, Ogata M, Utsumi K. Effects of aromatic bromine compounds on the function of biological membranes. Toxicol Appl Pharmacol. 1979;48(3):467–77.

    Article  PubMed  CAS  Google Scholar 

  • Jobling S, Nolan M, Tyler CR, Brighty G, Sumpter JP. Widespread sexual disruption in wild fish. Environ Sci Technol. 1998;32:2498–506.

    Article  CAS  Google Scholar 

  • Krishnan AV, Stathis P, Permuth SF, Tokes L, Feldman D. Bisphenol-A: an estrogenic substance is released from polycarbonate flasks during autoclaving. Endocrinology. 1993;132(6):2279–86.

    Article  PubMed  CAS  Google Scholar 

  • Kuiper GG, Carlsson B, Grandien K, et al. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology. 1997;138(3):863–70.

    Article  PubMed  CAS  Google Scholar 

  • Körner W, Hanf V, Schuller W, Bartsch H, Zwirner M, Hagenmaier H. Validation and application of a rapid in vitro assay for assessing the estrogenic potency of halogenated phenolic chemicals. Chemosphere. 1998;37:2395–407.

    Article  PubMed  Google Scholar 

  • Madeddu L, Legros N, Devleeschouwer N, Bosman C, Piccart MJ, LeClercq G. Estrogen receptor status and estradiol sensitivity of MCF-7 cells in exponential growth phase. Eur J Cancer Clin Oncol. 1988;24(3):385–90.

    Article  PubMed  CAS  Google Scholar 

  • Masiakowski P, Breathnach R, Bloch J, Gannon F, Krust A, Chambon P. Cloning of cDNA sequences of hormone-regulated genes from the MCF-7 human breast cancer cell line. Nucleic Acids Res. 1982;10(24):7895–903.

    PubMed  CAS  Google Scholar 

  • Nagel SC, Vom SF, Thayer KA, Dhar MG, Boechler M, Welshons WV. Relative binding affinity—serum modified access (RBA-SMA) assay predicts the relative in vivo bioactivity of the xenoestrogens bisphenol A and octylphenol. Environ Health Perspect. 1997;105(1):70–6.

    PubMed  CAS  Google Scholar 

  • Olea N, Pulgar R, Perez P, et al. Estrogenicity of resin-based composites and sealants used in dentistry. Environ Health Perspect. 1996;104(3):298–305.

    PubMed  CAS  Google Scholar 

  • Sellström U, Jansson B. Analysis of tetrabromobisphenol A in a product and environmental samples. Chemosphere. 1995;31:3085–92.

    Article  Google Scholar 

  • Sonnenschein C, Olea N, Pasanen ME, Soto AM. Negative controls of cell proliferation: human prostate cancer cells and androgens. Cancer Res. 1989;49(13):3474–81.

    PubMed  CAS  Google Scholar 

  • Soto AM, Sonnenschein C. The role of estrogens on the proliferation of human breast tumor cells (MCF-7). J Steroid Biochem. 1985;23(1):87–94.

    Article  PubMed  CAS  Google Scholar 

  • Soto AM, Lin T-M, Justicia H, Silvia RM, Sonnenschein C. An “in culture” bioassay to assess the estrogenicity of xenobiotics (E-Screen). In: Colborn T, Clement C, eds. Chemically-induced alterations in sexual and functional development: the wildlife/human connection. Princeton: Princeton Scientific Publishing; 1992:295–309.

    Google Scholar 

  • Soto AM, Chung KL, Sonnenschein C. The pesticides endosulfan, toxaphene, and dieldrin have estrogenic effects on human estrogen-sensitive cells. Environ Health Perspect. 1994;102(4):380–3.

    PubMed  CAS  Google Scholar 

  • Soto AM, Sonnenschein C, Chung KL, Fernandez MF, Olea N, Serrano FO. The E-SCREEN assay as a tool to identify estrogens: an update on estrogenic environmental pollutants. Environ Health Perspect. 1995;103(supplement 7):113–22.

    PubMed  CAS  Google Scholar 

  • Soto AM, Fernandez MF, Luizzi MF, Oles KA, Sonnenschein C. Developing a marker of exposure to xenoestrogen mixtures in human serum. Environ Health Perspect. 1997;105(supplement 3):647–54.

    PubMed  CAS  Google Scholar 

  • Soto AM, Michaelson CL, Prechtl NV, et al. Assays to measure estrogen and androgen agonists and antagonists. Adv Exp Med Biol. 1998;444:9–23.

    PubMed  CAS  Google Scholar 

  • Stancel GM, Boettger-Tong HL, Chiappetta C, et al. Toxicity of endogenous and environmental estrogens: what is the role of elemental interactions? Environ Health Perspect. 1995;103(supplement 7):29–33.

    PubMed  CAS  Google Scholar 

  • Sterzel W, Bedford P, Eisenbrand G. Automated determination of DNA using the fluorochrome Hoechst 33258. Anal Biochem. 1985;147(2):462–7.

    Article  PubMed  CAS  Google Scholar 

  • Toppari J, Skakkebaek NE. Sexual differentiation and environmental endocrine disrupters. Baillières Clin Endocrinol Metab. 1998;12(1):143–56.

    Article  PubMed  CAS  Google Scholar 

  • Villalobos M, Olea N, Brotons JA, Olea-Serrano MF, Ruiz dAJ, Pedraza V. The E-screen assay: a comparison of different MCF7 cell stocks. Environ Health Perspect. 1995;103(9):844–50.

    PubMed  CAS  Google Scholar 

  • White R, Jobling S, Hoare SA, Sumpter JP, Parker MG. Environmentally persistent alkylphenolic compounds are estrogenic. Endocrinology. 1994;135(1):175–82.

    Article  PubMed  CAS  Google Scholar 

  • WHO Working Group. Tetrabromobisphenol A. Environ Health Criteria. 1995;172:23–64.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Samuelsen, M., Olsen, C., Holme, J. et al. Estrogen-like properties of brominated analogs of bisphenol A in the MCF-7 human breast cancer cell line. Cell Biol Toxicol 17, 139–151 (2001). https://doi.org/10.1023/A:1011974012602

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1011974012602

Navigation