You are here:
Modeling the interaction of binary and ternary mixtures of estradiol and bisphenol A or its analogues in an in vitro estrogen mediated transcriptional activation assay (T47D-KBlue).
Citation:
Bermudez, D., L. E. GRAY, AND V. S. WILSON. Modeling the interaction of binary and ternary mixtures of estradiol and bisphenol A or its analogues in an in vitro estrogen mediated transcriptional activation assay (T47D-KBlue). Presented at Society of Toxicology 49th Annual meeting, Salt Lake City, UT, March 07 - 11, 2010.
Impact/Purpose:
Although several studies have investigated the estrogenic effects ofbisphenol A in vitro, few address whether the estrogenic activity of bisphenol A fimctions in a dose-additive manner with endogenous estrogens.
Description:
Bisphenol A is a ubiquitous monomer used to manufacture polycarbonate plastics. Exposure ofhuman and wildlife populations to bisphenol A and its analogs is widespread and well documented. Bisphenol A is hypothesized to be estrogenic in both in vivo and in vitro studies and has been shown to bind to estrogen receptors a and fJ to induce estrogenic activity via estrogen response elements. The current study tests binary and ternary mixtures ofan endogenous estrogen (estradiol-17fJ) with bisphenol A or its analogues tetrabromo-bisphenol A or bisphenol AF and evaluates their interaction across a range ofconcentrations to determine if the mixtures emulate a dose-addition model ofinteraction. The T47D-KBluc estrogenresponsive transcriptional activation luciferase reporter gene assay was used to determine a full dose-response and obtain ECso and HillSlope datafor the mixture chemicals tested. ECso and HillSlope dataare as follows: estradiol-17fJ, 5.47Ie-13, 0.7542; bisphenol A, 7.226e~, 1.108; and bisphenol AF, 2.045e~, 1.106. Tetrabromo-bisphenol A induced no estrogenic dose response on the T47D-KBluc assay and no ECso or HillSlope was calculated for it. ECso and HillSlope datawere incorporated into a dose addition model to predict responses for binary mixtures of estradiol and bisphenol A1bisphenol AF in an eight by eight factorial design and for ternary mixture ofestradiol, bisphenol A and bisphenol AF in a four by four by four factorial design. Both the binary mixturesand the ternary mixture behaved in a dose-additive manner and were well predicted by the dose-addition model. Although several studies have investigated the estrogenic effects ofbisphenol A in vitro, few address whether the estrogenic activity of bisphenol A fimctions in a dose-additive manner with endogenous estrogens. Understanding the behaviorofmixtureinteractions ofbisphenolA withendogenousestrogenswill allowusto better gauge the threat oflow-dose exposure to bisphenol A and its analogues