[[alternative]]Effects of Arsenics on Cell Growth and Estrogen Receptor-αExpression in MCF-7 Breast Cancer Cells

[[abstract]]Inorganic arsenics, the common environmental pollutants, are widely dispersed and the well-documented human carcinogens associated with cancers of skin, lung and bladder and can induce cytotoxicity, chromosomal abnormalities, oxidative stress, altered DNA repair, altered growth factors etc. Several reports indicated that inorganic arsenic might somehow act through an estrogenic mode of action. In this study, effects of sodium arsenite and sodium arsenate on cytotoxicity, cell proliferation and the expression of estrogen receptorα(ERα) in breast adenocarcinoma MCF-7 cells are determinated. The preliminary results show that the inhibiting threshold concentrations of sodium arsenite and sodium arsenate on cell growth are at 1μM and 10μM, respectively, whereas their concentrations lower than inhibiting threshold concentrations promoted cell growth instead of cell toxicity. Time course studies on cells treated with 0.1~1μM sodium arsenite and 1~10μM sodium arsenate for 24 h, and observed consecutive six days without drugs, MCF-7 cells proliferation exhibited continuous increase. Cotreated with drugs and estrogen antagoist (ICI 182,780), MCF-7 cell proliferations were completely inhibited. Data of Western blotting show that the expression of ERα were decreased in cells treated with low dose of sodium arsenite and sodium arsenate, but expression of estrogen receptorβ were not affected. Immunocytochemical studies with fluorescent microscopy illustrated that ERα displayed a diffusion distribution in cytoplasm and were more concentrated within nucleus of control cell and E2-treated cells. In arsenic-treated cells, the ERαonly displayed in cytoplasm. Whole-cell competitive estrogen-receptor binding assay demonstrate that 0.1, 0.5 and 1μM sodium arsenite could bound with 28%, 35% and 48% in ER respectively. In this study it was concluded that arsenite could bind with estrogen receptor. Based on results above, MCF-7 cells treated with a low dose sodium arsenite and sodium arsenate affect cell proliferation, ERαexpression, and competition of estrogen receptor binding；and indicate that inorganic arsenics do have the characteristics of environmental hormone for inducing physiological effect, through a estrogen model.