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Modeling the interaction of binary mixtures of estradiol and bisphenol A or its analogues in an in vitro estrogen mediated transcriptional activation assay (T47D-KBIuc).
Citation:
Bermudez, D., L. E. GRAY, AND V. S. WILSON. Modeling the interaction of binary mixtures of estradiol and bisphenol A or its analogues in an in vitro estrogen mediated transcriptional activation assay (T47D-KBIuc). Presented at Triangle Consortium of Reproductive Biology Meeting, RTP, NC, January 30, 2009.
Impact/Purpose:
To present at the Triangle Consortium of Reproductive Biology Meeting
Description:
Bisphenol A (BPA) is a ubiquitous monomer used to manufacture polycarbonate plastics. BPA is used in composites and sealants in dentistry, for epoxy resins used as protective liners in metallic cans, and as additives in various plastics. Approximately 1.7 billion pounds of BPA are produced in the US per year, designating BPA a high production volume chemical. Exposure of BPA and its analogs to human and wildlife populations is widespread and well documented. In the US, BPA surface water sample concentrations range between non-detectable and 12 μg/L with a median of 0.14 μg/L. The general population averages urinary total BPA concentration ranged between 1.5-15.9 μg/L with an extrapolated daily intake of BPA ranging from .008-1.5 μg/kg bw/dy. Infants, a higher risk population for exposure and effects of BPA., are exposed to breast milk with free BPA as high as 6.3 μg/L and an estimated daily intake of approximately 1 μg/kg bw/dy in the US. BPA has been shown to have endocrine activity and is hypothesized to be estrogenic in both in vivo and in vitro studies. Previous studies have established that BPA binds to ERα and ERβ to induce estrogenic activity via estrogen response elements. The current study will test binary mixtures of an endogenous estrogen (estradiol-17β, E2) with BPA and evaluate their interaction across a range of concentrations. T47D-KBluc estrogen-responsive luciferase reporter gene assay on 96 well plate was used to determine a full dose-response and obtain EC50 and Hillslope data for E2 (2.52e-l2 M, 1.507) and BPA (3.32ee-7 M, 1.805). EC50 and Hillslope data was incorporated into a dose addition model to predict responses for binary mixtures of six E2 concentrations each with six BPA concentrations in order to develop a surface response plot. Modeled predictions will be tested experimentally to determine if the mixtures emulate a dose addition model of interaction. Although several studies have investigated the estrogenic effects of BPA in vitro, few address whether the estrogenic activity of BPA functions in a dose-additive manner with endogenous estrogens. Understanding the behavior of mixture interactions of BPA with endogenous estrogens will allow us to better gauge the threat of low-dose exposure of BPA (for in vitro, ≤1x10-7 M ). Future studies will examine additional mixtures of estrogens including BPA analogues (TBBPA or BPAF).