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(055) Environmental bisphenols interact in the estrogen receptor signal transduction pathway in breast cancer cells. Fernandez, M.F.1, Rivas, A.M.1, Pulgar, R.1, Leclercq, G.2, Metzler, M.3, Villalobos, M.1, Olea, N.1, Pedraza, V.1, 1 2 3 ABSTRACT- Bisphenols and stilbenes demonstrated their estrogenicity in vivo in 1936 with reports on the increase in uterine weight in rats after treatment with compounds containing two phenolic rings with hydroxyl groups in para positions. The stilbene diethylstilbestrol had pharmaceutical utility as a synthetic estrogen and bisphenols occupy a predominant position in the plastic industry. We compared estradiol and different bisphenols (A basic bis-hydroxyphenyl structure to which we added to the central carbon alkanes -ethane to heptane--, ketone, propanol, perfluoropropane and methyphenol) in the estrogen receptor transduction signal pathway in MCF-7 cells: i) Induction of mRNA of pS2, ii) Induction of the luciferase reporter gene placed under an estrogen-responsive element (ERE) in the MVLN cell line derived from MCF-7 cells, iii) Quantification of the estrogen induced progesterone receptor, iv) Quantification of the secreted pS2 protein, and v) Cell proliferation in the E-Screen bioassay. All the bisphenols tested elicited a full agonist response in all the assays. However some differences were found in: i) The concentration needed to induce a full estrogenic response (Potency), ii) The response range observed for estradiol and the bisphenols (Efficiency), and iii) The amplitude of response, enabling differentiation between an agonist, partial agonist and nil effect. This study demonstrates that bisphenols exerted estrogenic responses at different levels in the estrogen receptor transduction signal pathway but at higher concentrations than endogenous estrogens. The proliferation bioassay (E-Screen) was the most sensitive and effective among the four assays used. Key words: bisphenols, estrogen receptor, pS2 |
