Possible estrogenic effects of some higly bioaccumulated polychlorinated biphenyls (PCB101, 118,138,153) alone and in mixture in MCF-7 breast cancer cells

Polychlorinated biphenyls (PCBs) are ubiquitous environmental persistent contaminants giving rise to potential health hazard. Depending on the position and number of chlorine substitutions, different classes of PCB congeners elicit a complex spectrum of biological and toxic responses in a number of models in vivo and in vitro. Moreover, some PCBs have been shown to have potential estrogen and anti-estrogen effects. In the present study we have analysed the potential estrogenic effect in MCF-7 cells of four very biologically relevant PCB congeners alone and in mixture: PCB 101 (2,2′,4,5,5′-pentachlorobiphenyl), PCB 118 (2,3′,4,4′,5-pentachlorobiphenyl), PCB 138 (2,2′,4,4′,5,5′-hexachlorobiphenyl) and PCB 153 (2,2′,3,4′,5,5′-heptachlorobiphenyl). The mixture of four PCBs was tested at seven different concentration chosen on the basis of their recovery from crop and some foods. The ability of these PCBs alone and in mixture to induce cell proliferation and the level of estrogen-regulated protein pS2 were studied using the human MCF-7 breast cancer cells. In this cell line, only PCB 153 (35 μM) stimulates cell proliferation from 48 h up to 6th day, while PCB 118 (40 μM) only at 48 h. No effect was observed after treatment with PCB 101 (45 μM) and PCB 138 (10 μM) until 6 days. The treatment with different mixture concentrations causes a significant decrease of cell proliferation at different time. No variation of pS2 level was observed after treatment with the different PCBs alone and in mixture. In exploring the molecular mechanism and the kinetic of these events, we found that PCB 153 was able to induced mitogen-activated protein kinase (MAPK) ERK1/2 at 4, 8 and 12 h, while the anti-proliferative effect seems to be mediated by an apoptotic action beginning at 12 and ending at 48 h