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Modeling the interaction of binary and ternary mixtures of estradiol with bisphenol A and bisphenol A F in an in vitro estrogen mediated transcriptional activation assay (T47D-KBluc).
Citation:
Bermudez, D., L. E. GRAY, AND V. S. WILSON. Modeling the interaction of binary and ternary mixtures of estradiol with bisphenol A and bisphenol A F in an in vitro estrogen mediated transcriptional activation assay (T47D-KBluc). TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 116(2):477-487, (2010).
Impact/Purpose:
Mixture modeling of environmental estrogens and estradiol with in vitro ER-mediated assay. Manuscript compares two additivity prediction models.
Description:
Humans are concurrently exposed to xenoestrogens and to physiological levels of endogenous estrogens. Endogenous estrogen levels vary from low levels in infants 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-l Zf (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 (8x8 factorial) and ternary (4x4x4 factorial) mixtures of an endogenous estrogen (E2) interact with BPA and/or, BPAF. Log ECso and Hillslope values with standard errors, respectively, for individual compounds were as follows: E2, -12.10 M± 0.06071, 0.7702 ± 0.1739; BPA, -6.679 M± 0.08505, 1.194 ± 0.2137; and BPAF, -7.648 M ± 0.05527,1.273 ± 0.1739. TBBPA was not evaluated in mixture studies because of its minimally estrogenic response at 3e-s M and 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. Overall, 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 to the potential risk of exposure to these chemicals, individually or as mixtures.
