Investigation of the effects of bisphenol A and its analogs on endoplasmic reticulum stress in cell culture

Bisphenol A (BPA) and its analogs bisfenol F (BPF) and bisfenol S (BPS) are endocrine disrupting chemicals widely used in industry. It has high risks, especially for human health, because it is found in many products used in daily life and contaminates water. In doctorate thesis, the toxicological effects of BPA, BPF and BPS on endoplasmic reticulum (ER) stress and their possible relationship with ER stress pathways have been investigated in PC-3 and PNT1A cells. In PC-3 cells, IC50 values were determined for BPA, BPF and BPS respectively;157,66 µM, 510,17 µM and 519,6 µM after 48 h of exposure; in PNT1A cells, the IC50 values were determined for BPA, BPF and BPS respectively; 101,05 µM, 485,5 µM and 659,24 µM after 48 h of exposure. In the cell proliferation determined by BrdU test, after 48 hof exposure to BPA, BPF and BPS at 1-10 µM concentrations, a significant increase was observed in PC-3 cells at the rate of 10-41,85%; a significant decrease of 29,7% was determined in PNT1A cells after only 10 µM BPA exposure. In ROS formation, non-significant changes were observed in PNT1A and PC-3 cells compared to control. In addition, after 48 h of exposure to 0,1-10 µM BPA, BPF and BPS, significant differences were observed in PC-3 cells;16,2-22,14% in late apoptosis; significant differences were observed in PNT1A cells, 21,27% in late apoptosis compared to the control. Furthermore, exposure to BPA, BPF and BPS at 1-10 µM concentrations,in both PC-3 and PNT1A cells have shown significantly alterations of expression levels in the ER stress-related genes (PERK, EIF2α, IRE1α, CHOP, GRP78, ATF4, ATF6) and genes involved in apoptosis (BAX, BCL-2 XIAP, AIF, CASPASE-9). In addition, exposure to BPA, BPF and BPS at concentrations of 1-10 µM was found to cause significant changes on CHOPprotein by western blot technique. According to the results obtained from the thesis study, it is suggested that BPA and its analogs may have toxic effects through cellular stress and apoptotic mechanisms, and BPA may be more effective than BPF and BPS; it is expected that results from this thesis will contribute to the literature on the effects of endocrine disruptors on ER stress mechanisms.