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EFFECT OF EXPOSURE PROTOCOL AND HEAT SHOCK PROTEIN EXPRESSION ON ARSENITE INDUCED GENOTOXICITY IN MCF-7 BREAST CANCER CELLS
Citation:
Barnes, J A., B W. Collins, D J. Dix, AND J W. Allen. EFFECT OF EXPOSURE PROTOCOL AND HEAT SHOCK PROTEIN EXPRESSION ON ARSENITE INDUCED GENOTOXICITY IN MCF-7 BREAST CANCER CELLS. Presented at 2001 Environmental Mutagen Society 32nd Annual Meeting, San Diego, CA, March 16-21, 2001.
Description:
Effect of exposure protocol and heat shock protein expression on arsenite induced genotoxicity in MCF-7 breast cancer cells
The genotoxic effects of arsenic (As) are well accepted, yet its mechanism of action is not clearly defined. Heat-shock proteins (HSPs) protect against the toxic effects of heat but it is unclear if HSP induction offers protection against DNA damage induced by As. This study was designed to investigate the genotoxicity of high dose/short exposures vs. low dose/long exposures of As in MCF -7 cells that express different levels of inducible HSP70. A tetracycline-regulated gene expression system was used to expose HSP70 ON and OFF cells to As using either a low dose/long exposure protocol (0,5 f-tM and 10 f-tM for 46 hrs) or a high dose/short exposure protocol (0, 10 f-tM and 40 f-tM for 8 hrs). The genotoxicity of As was evaluated using a cytokinesis-block micronucleus (MN) assay. Kinetochore (K) staining of MN provided additional information to differentiate the origins of MN. Dose-dependent increases in the percent of micronucleated binucleated cells were observed following As exposure by both protocols. However, induction levels of MN were significantly lower in cells expressing elevated HSP70 as compared to cells that expressed control levels of HSP70 (p< 0.05). While increases in K positive and K negative MN were observed by both protocols, the low dose protocol demonstrated a significantly higher induction of K positive MN as compared to the high dose protocol. Relationships between these chromosomal effects and altered expression of DNA damage and repair genes are being assessed by gene array analysis. Overall, our data suggest that differences in the dose and time of exposure may alter the type of cellular damage inflicted by As and that HSP70 plays a role in protecting cells from As induced genotoxicity.
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