Journal Article

Modeling the Interaction of Binary and Ternary Mixtures of Estradiol with Bisphenol A and Bisphenol AF in an <i>In Vitro</i> Estrogen-Mediated Transcriptional Activation Assay (T47D-KBluc)

Dieldrich S. Bermudez, Leon E. Gray and Vickie S. Wilson

in Toxicological Sciences

Volume 116, issue 2, pages 477-487
Published in print August 2010 | ISSN: 1096-6080
Published online May 2010 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfq156
Modeling the Interaction of Binary and Ternary Mixtures of Estradiol with Bisphenol A and Bisphenol AF in an In Vitro Estrogen-Mediated Transcriptional Activation Assay (T47D-KBluc)

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Exposure to xenoestrogens occurs against a backdrop to physiological levels of endogenous estrogens. Endogenous estrogen levels vary from low levels in early childhood to high levels during pregnancy and in young women. However, few studies have addressed how xenoestrogens interact with endogenous estrogens. The current study was designed to characterize the individual dose-response curves of estradiol-17β (E2), bisphenol A (BPA), tetrabromo-bisphenol A (TBBPA), and bisphenol AF (BPAF, 4,4'-hexafluoroisopropylidene diphenol) on estrogen-dependent luciferase expression in T47D-KBluc cells and to determine how binary (8 × 8 factorial) and ternary (4 × 4 × 4 factorial) mixtures of an endogenous estrogen (E2) interact with BPA and/or BPAF. Log EC50 and hillslope values with SEs, respectively, for individual compounds were as follows: E2, −12.10M ± 0.06071, 0.7702 ± 0.1739; BPA, −6.679M ± 0.08505, 1.194 ± 0.2137; and BPAF, −7.648M ± 0.05527, 1.273 ± 0.1739. TBBPA was not evaluated in mixture studies because of its minimally estrogenic response at 3 ×10−5M and elicited cytotoxicity at higher concentrations. Both the binary mixtures of E2 with BPA and BPAF and the ternary mixture of E2, BPA, and BPAF behaved in an additive manner. For binary mixtures, as E2 concentration increased, higher concentrations of BPA and BPAF were necessary to induce a significant increase in the estrogenic response. Understanding the behavior of mixture interactions of xenoestrogens, like BPA and BPAF, with endogenous estrogens will allow a better assessment of the potential risk associated with exposure to these chemicals, individually or as mixtures.

Keywords: in vitro; mixtures; estradiol; bisphenol A; mixtures; bisphenol AF

Journal Article.  5419 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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