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COMPARISON OF GENE EXPRESSION IN KIDNEY AND URINARY BLADDER FROM RATS TREATED WITH DIMETHYLARSINIC ACID
Citation:
Bailey, K. A., S D. Hester, A. Wang, J. L. Robertson, D C. Wolf, AND B. Sen. COMPARISON OF GENE EXPRESSION IN KIDNEY AND URINARY BLADDER FROM RATS TREATED WITH DIMETHYLARSINIC ACID. Presented at Society of Toxicology, New Orleans, LA, March 6-10, 2005.
Description:
Arsenic is widespread in the environment and a human carcinogen. A major metabolite of inorganic arsenic (iAs) in most species, including humans, is dimethylarsinic acid (DMA), which is also used as a pesticide. Unlike iAs, DMA induces urinary bladder tumors in rats. DMA is believed to induce bladder cancer through a combination of target cell cytoxicity, oxidative stress, and DNA damage. We propose that these effects are specific to the cancer target cell and not a general feature of DMA exposure. The present study compares the gene expression associated with DMA exposure in kidney to a previous examination of the rat transitional epithelium lining the urinary bladder. Female F344 rats were treated in the drinking water with 1, 4, 40, or 100 ppm DMA for 4 weeks. The rats were euthanized and kidneys were taken for histology and RNA extraction for 2dye custom spotted microarray analysis. There was no significant renal histopathology whereas the urinary bladder had dose-dependent cytotoxicity. Microarray analysis of the transitional epithelia showed that DMA treatment altered the expression of apoptosis, cell cycle regulation, proliferation, signal transduction and oxidative stress response genes. The major functional categories affected in the kidney were genes that control metabolism, particularly lipid metabolism. The differental gene expression profiles between cancer target and non-target tissues suggest events in target tissues associated with DMA-induced carcinogenesis can be determined.