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GENE EXPRESSION PROFILING OF THE RAT KIDNEY FOLLOWING CHRONIC EXPOSURE (100 WKS) TO THE WATER DISINFECTANT BYPRODUCT AND RENAL CARCINOGEN, POTASSIUM BROMATE.
Citation:
Delker, D. A., J W. Allen, G M. Nelson, T. M. Moore, B C. Roop, R D. Owen, AND A B. DeAngelo. GENE EXPRESSION PROFILING OF THE RAT KIDNEY FOLLOWING CHRONIC EXPOSURE (100 WKS) TO THE WATER DISINFECTANT BYPRODUCT AND RENAL CARCINOGEN, POTASSIUM BROMATE. Presented at AACR, Orlando, FL, March 27-31, 2004.
Description:
Gene expression profiling of the rat kidney following chronic exposure (100 wks) to the water
disinfectant byproduct and renal carcinogen, potassium bromate.
Don Delker, James Allen, Gail Nelson, Tanya Moore, Barbara Roop, Russell Owen, and Anthony DeAngelo. Environmental Carcinogenesis Division, National Health and Environmental Effects Research Laboratory, U. S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Potassium bromate (KBrO3) is a chemical oxidizing agent that has been used extensively in the food and cosmetic industries. KBrO3 is also found in drinking water as a disinfection byproduct of surface water ozonation. Chronic exposures to KBrO3 cause renal cell tumors in rats, hamsters and mice and thyroid and testicular mesothelial tumors in rats. As an adjunct to a rat carcinogenicity assay of bromate, we characterized gene expression profiles related to carcinogenic exposures. F344 rats were administered KBrO3 in the drinking water at concentrations of 0.1 and 0.4 g/L for 100 weeks. Kidney tumor incidence reached approximately 10% in the 0.1 g/L dose group and 40% in the 0.4g/L dose group. Three control kidneys and two kidneys each from the 0.1, and 0.4 g/L groups were used to prepare total RNA, double stranded cDNA, and amplified RNA (aRNA) for labeling and hybridization to glass slide oligo microarrays. aRNA was also prepared from two kidney adenomas, one from each dose group. KBrO3-induced changes in gene expression were determined using a modified t-test and multiple clustering analyses. Transcripts considered differentially expressed had a p-value < 0.05 and
a fold change 2. Approximately 70 genes, out of 2200 found present on all arrays analyzed, were differentially expressed with respect to KBrO3 treatment. Twenty of those genes were also differentially expressed in the kidney adenomas. These transcripts were further classified according to biological function which included stress responses, transcription regulation, and dedifferentiation. Although HSP70/HSP90 organizing protein transcripts were up regulated (2-fold) in both treated kidney and tumor tissue in agreement with previous acute exposures in rat mesothelial cells (Crosby et al, 2000), no change was observed in kidney HSP70 transcripts following chronic exposures. Transcription proteins and dedifferentiation markers up regulated in treated kidney and tumors included polymerase II (5-fold), Pet-1 (3-fold) and carcinoembryonic antigen (CGM3, 5-fold), respectively. These and other identified transcripts may be useful biomarkers of chronic KBrO3 exposures and potentially aid in the cancer risk assessment of this drinking water contaminant. [This abstract does not necessarily reflect EPA policy]