Combined effect of xenoestrogens and growth factors in two estrogen-responsive cell lines

It is now well recognized that estrogenic signaling mechanisms are far more complex than once thought. Several crosstalks between the estrogen receptor and other signaling pathways may influence the estrogenic stimulation of cell growth. Thus, the estrogenic effects of several environmental contaminants, now suspected to act as endocrine disrupters, may be influenced by a simultaneous stimulation of other signaling pathways. The aim of this study was to investigate whether the growth response of two estrogen-responsive cell lines, MCF-7 and GH3, treated with xenoestrogens might be affected by the addition of growth factors to their culture medium. Cells were treated with two known xenoestrogens, endosulfan and chlordane, alone or in the presence of insulin-like growth factor-1 and epidermal growth factor, respectively, and their growth was measured using the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxyanilide proliferation assay. Our results show that treatment with endosulfan or chlordane as well as treatment with growth factors increased cell growth, while the administration of xenoestrogens together with growth factors triggered a partly additive response with no antagonist or synergistic effect. These results sustain a role for xenoestrogens in cellular growth.