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ELEVATED LEVELS OF INDUCIBLE HEAT SHOCK PROTEIN (HSP70-1) PROTECT MCF-7 CELLS FROM ARSENITE TOXICITY
Barnes, J, D J. Dix, B W. Collins, J B. Garges, AND J W. Allen. ELEVATED LEVELS OF INDUCIBLE HEAT SHOCK PROTEIN (HSP70-1) PROTECT MCF-7 CELLS FROM ARSENITE TOXICITY. Presented at Society of Toxicology Annual Meeting, Philadelphia, Pennsylvania, March 19-23, 2000.
Heat shock proteins (HSPs) belong to the highly conserved family of stress proteins and are induced following exposure to arsenic. Elevated HSPs protect against cellular damage from heat but it is unclear whether HSP induction alters the damaging effects of environmental chemical contaminants. Therefore, this study was designed to Investigate the effects of sodium arsenite (As) in MCF-7 cells that overexpress Inducible HSP70 (HSP70-1). A tetracycline-controlled expression system was developed to regulate HSP70-1 levels. Clonel4 (C14) cells exhibited the highest Induction of HSP70-1 in the absence of doxycydine ("ON") and HSP70-1 could be down-regulated to control levels In the presence of doxycydine ("OFF"). In order to examine the cytotoxic and genotoxic effects of sodium arsenite, C14ON and C14OFF cells were exposed to either 0 (control), 5 uM or 10 uM As. For cytotoxidty studies, cells were exposed for 24 hours and assayed for viability and apoptosis using acridine orange and ethidium bromide staining. Both C14ON and C14OFF cells showed a dose-dependent decrease In cell viability and Increase In apoptosis in response to arsenite. Cells expressing elevated HSP70-1 were significantly less affected (i.e. higher viability, lower apoptosis) than cells that did not overexpress HSP70-1. The genotoxicity of arsenite was evaluated using a cytokinesis-block micronucleus (MN) assay. MN were Induced In both C14ON and C14OFF cells in response to As. However, induction levels of MN were significantly lower in HSP70-1 overexpressing cells as compared to cells that expressed control levels of HSP70-1 (p< 0.05). Collectively, these data demonstrate a protective effect of HSP70-l expresslon on the cytotoxic and genotoxic effects of arsenite In MCF-7 cells.
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
ENVIRONMENTAL CARCINOGENESIS DIVISION
GENETIC AND CELLULAR TOXICOLOGY BRANCH