Endocrine Abstracts

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 (1×10⁻⁶–1×10⁻¹²M) and time (24–120 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 (80–130%). 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.