Abstract 540: Increased growth and malignant transformation of human prostate epithelial cells by chronic exposure to arsenic and estrogen

Both Arsenic and 17β-estradiol have been shown to induce growth and neoplastic formations in prostate epithelial cells. Estrogens are involved in prostate development and function at several stages. Arsenic has mild estrogenic properties. However, the effects of the co-exposure to physiologically relevant doses of these two chemicals on human prostate epithelial cells are not known. We hypothesize that as compared to the individual exposure, the co-exposure to arsenic and estrogen will potentiate the cell growth and transformation in prostate epithelial cells. Therefore, the objective of this study was to examine the effects of chronic exposure to arsenic and estrogen both individually and in combination on neoplastic transformations and increase cell growth. Human prostate epithelial cells, RWPE-1 were treated for 6 months with sodium-meta arsenite and 17β-estradiol both alone and in combination at concentrations of 100 pg/mL and 100 ng/mL. These treated cells were maintained further for 3 months in culture media without arsenic or estrogen supplementation. The effects of these compounds on cell growth were determined by cell count and MTT assay, and malignant transformation of cells was determined by anchorage independent growth assay on soft agar. The mitogenic effects of these chemicals were further confirmed at molecular level by cell cycle analysis using flow cytometry and gene expression analysis by quantitative real time PCR. The result of this study revealed that chronic exposure to arsenic and estrogen causes increased cell proliferation and induces cell transformation as observed in colony formation assay. The combination of these two chemicals had potentiating effects on cell growth and transformation of RWPE-1 cells. The increased percentage of cells in S-phase and increased expression of CyclinD1 as well as the anti-apoptotic gene Bcl2 further confirmed the mitogenic potential of these two chemicals in RWPE-1 cells. The present findings of increased growth and transformation of arsenic and estrogen treated cells and epigenetic changes observed in these cells together suggest that these carcinogenic chemicals induce malignant transformation in prostate epithelial cells at least in part through epigenetic mechanisms. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Sup