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INDUCTION OF CELL PROLIFERATION AND APOPTOSIS IN HL60 AND HACAT CELLS BY ARSENIC, ARSENATE, AND ARSENIC-CONTAMINATED DRINKING WATER
Citation:
Mumford, J. S., M Schmitt, AND J. Zhang. INDUCTION OF CELL PROLIFERATION AND APOPTOSIS IN HL60 AND HACAT CELLS BY ARSENIC, ARSENATE, AND ARSENIC-CONTAMINATED DRINKING WATER. Presented at American Association of Cancer Research, San Francisco, CA, April 6-10, 2002.
Description:
Induction of cell proliferation and apoptosis in HL-60 and HaCaT cells by arsenite, arsenate and arsenic-contaminated drinking water. T-C. Zhang, M. Schmitt, J. L. Mumford National Research Council, Washington DC and U.S. Environmental Protection Agency, NHEERL, Research Triangle Park, NC
It is known that arsenic is a human carcinogen and also an anticancer agent. Research is needed for the mode of actions for arsenic carcinogenesis and also assessing the shape of dose-response curve at low doses in humans. In this study we investigated the effects of sodium arsenite, sodium arsenate and arsenic-contaminated drinking water on induction of cell proliferation and apoptosis in HaCaT (human skin keratinocytes) and HL-60 cells (human acute promyelocytic leukemia). Cellular proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays following exposure to arsenite, arsenate and arsenic-contaminated water from Inner Mongolia (in progress). Apoptosis was determined by Hoechst/PI nuclei staining and DNA ladder assay. In both cell lines after 48 h exposure, arsenite enhanced cellular proliferation at low concentrations (0.1- 0.8 M) with maximal increase (29-30% of control cells) at 0.8 and 0.5 m for HaCaT and HL60, respectively. However, arsenite inhibited proliferation at high concentrations (1-40 M), with 50% inhibition at 4.0 and 2.5 M for HaCaT and HL-60, respectively. Apoptosis (16-18%) was observed starting at 1 M of arsenite in both cell lines. Similar responses were also found with arsenate-treated cells, except that arsenate required higher concentrations to induce cell proliferation and apoptosis in both cell lines. The results showed that arsenite and arsenate promoted human cell proliferation at low concentrations but induced apoptosis at high concentrations. This may have implication that exposure to arsenic induced cancers and exerted apoptotic effects in multiple tissue cells in humans. (This abstract does not reflect EPA policy.)
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