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KIDNEY TOXICOGENOMICS OF ACUTE SODIUM AND POTASSIUM BROMATE EXPOSURE IN F344 MALE RAT
Citation:
GETER, D., G. W. KNAPP, D. A. DELKER, M. H. GEORGE, A. B. DEANGELO, J. W. ALLEN, AND W. O. WARD. KIDNEY TOXICOGENOMICS OF ACUTE SODIUM AND POTASSIUM BROMATE EXPOSURE IN F344 MALE RAT. Presented at Society of Toxicology Annual Meeting 2007, Charlotte, NC, March 25 - 29, 2007.
Description:
Bromate, used in both the food and cosmetics industry, is a drinking water disinfection by-product that is nephrotoxic and carcinogenic to rodents. To gain insight into the carcinogenic mechanism of action, identify possible biomarkers of exposure, and determine if the cation, potassium, significantly alters gene expression, kidney gene expression was examined from male F344 rats exposed to NaBrO3 and KBrO3 in drinking water for 2 weeks. Total RNA was isolated from kidney samples and gene expression analyzed using Affymetrix Rat 230A 2.0 GeneChips. Gene expression patterns from two non-carcinogenic (1, and 20 ppm) and one carcinogenic dose (400 ppm) at 2 wk, were compared to each other and to previous gene expression from a 52 wk, 400 ppm KBrO3 study. Statistical analysis revealed 1, 167, and 229 genes in the NaBrO3 exposure group and 17, 195, and 139 differentially expressed genes (DEGs) in the KBrO3 exposure group at the low, medium, and high doses, respectively. Gene ontology classification of the Na- and KBrO3 groups showed similar expression alterations of genes involved in oxidative stress, lipid metabolism, kidney function/ion transport, and cellular function. Of these, all were equally affected except for an increase in kidney function/ion transport genes observed in the Na- versus KBrO3 (34 vs. 9 DEGs). In comparing DEGs from acute 400 ppm Na- (139 DEGs) and KBrO3 (229 DEG5) to the chronic 400 ppm KBrO3 (224 DEGs), there were 14 and 32 shared DEGs respectively that also matched in direction of change. Thus, this study identifies the potential for acute bromate gene expression profiles to forecast gene expression changes at chronic time points. However, the primary finding was that sodium and potassium bromate treated kidneys yield similar kidney gene expression profiles at two weeks exposure.