ECE2013 Poster Presentations Endocrine disruptors (11 abstracts)
Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
Endocrine disruptors represent exogenous substances that alter hormonal, reproductive, immune and homeostatic systems. Bisphenol-A (BPA) in the form of polymer is a part of polycarbonates used in plastics, food packing and medical devices. Incomplete BPA polymerization and cleavage of weak chemical bonds result in monomer release/leakage to the foods and beverages. Many studies have associated exposure to BPA with higher incidence of hormone-dependent mammary and prostate carcinomas. In present study we investigated the effect of BPA on proliferation of MCF-7 cells in cell culture. Dose (1×10−61×10−12M) and time (24120 h) dependent effects of BPA were compared with estradiol (E2) effects. Cell growth was measured by WST-1 test, de novo synthesis of DNA with BrdU incorporation to DNA, apoptotic proteins and cyclin-A were determined by Western blot. Compared to E2, high concentrations of BPA significantly stimulated cell growth after 48 h treatment. Long-term effect of BPA (96, 120 h) similarly stimulated cell proliferation (40%), however the impact did not achieve the effect of E2 (80130%). Stimulatory effect of BPA on cell proliferation (48 h) was accompanied by huge increase (~200%) of de novo DNA synthesis even after 24 h. At longer time expositions BPA effects significantly declined and were comparable with those of E2. BPA reduced expression of pro-apoptotic proteins p53 (48 h) and Bax (24 h) by dose dependent manner (vs E2), while expression of anti-apoptotic protein Bcl-2 was increased after 96 h only. BPA in low and high doses significantly reduced cyclin A protein expression as compared to E2. In conclusion, BPA effects on MCF-7 cells proliferation result from alteration of several cellular processes like synthesis DNA, disturbed synthesis/degradation of apoptotic proteins and proteins of cell cycle division and replication. Effects of BPA are dose-dependent. Supported by grants of VEGA 2/0107/10 and APVV 00147-10.