Journal
TOXICOLOGY LETTERS
Volume 199, Issue 2, Pages 153-159Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2010.08.017
Keywords
Autophagy; Arsenic; Lysosome; Microarray; Lymphoblastoid
Categories
Funding
- NIEHS [ES 00694, ES 04940, ES 16652]
- NIH [P30CA23074, ES06694]
- BIO5 Institute
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Chronic exposure to inorganic arsenic is associated with diverse, complex diseases, making the identification of the mechanism underlying arsenic-induced toxicity a challenge. An increasing body of literature from epidemiological and in vitro studies has demonstrated that arsenic is an immunotoxicant, but the mechanism driving arsenic-induced immunotoxicity is not well established. We have previously demonstrated that in human lymphoblastoid cell lines (LCLs), arsenic-induced cell death is strongly associated with the induction of autophagy. In this study we utilized genome-wide gene expression analysis and functional assays to characterize arsenic-induced effects in seven LCLs that were exposed to an environmentally relevant, minimally cytotoxic, concentration of arsenite (0.75 mu M) over an eight-day time course. Arsenic exposure resulted in inhibition of cellular growth and induction of autophagy (measured by expansion of acidic vesicles) over the eight-day exposure duration. Gene expression analysis revealed that arsenic exposure increased global lysosomal gene expression, which was associated with increased functional activity of the lysosome protease, cathepsin D. The arsenic-induced expansion of the lysosomal compartment in LCL represents a novel target that may offer insight into the immunotoxic effects of arsenic. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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