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GENE EXPRESSION ALTERATIONS OBSERVED IN PRIMARY CULTURED RAT HEPATOCYTES AFTER TREATMENT WITH CHLORINATED OR CHLORINATED AND OZONATED DRINKING WATER FROM EAST FORK LAKE, OHIO
Citation:
CROSBY, L., T. MOORE, J. E. SIMMONS, AND A B. DEANGELO. GENE EXPRESSION ALTERATIONS OBSERVED IN PRIMARY CULTURED RAT HEPATOCYTES AFTER TREATMENT WITH CHLORINATED OR CHLORINATED AND OZONATED DRINKING WATER FROM EAST FORK LAKE, OHIO. Presented at Society of Toxicology Annual Meeting, San Diego, CA, March 05 - 09, 2006.
Description:
Drinking water from East Fork Lake was spiked with iodide and bromide, disinfected with chlorine or ozone + chlorine, concentrated ~100-fold using reverse osmosis, and volatile disinfection by-products (DBPs) added back. Primary rat hepatocytes were exposed to full-strength, 1:10 or 1:20 dilutions of water for 24 hr. To examine the effects of concentrated DBPS (>500 identified) on rat hepatocytes, we used differential gene expression (DGE) to generate expression profiles. Lactate dehydrogenase (LDH) release was used to measure cell death, and a nitro-blue tetrazolium assay (MTS) was used to measure metabolic activation. LDH release was increased by both full-strength concentrates, indicating cytotoxicity. Diluted waters produced no increases in LDH release, but the MTS assay demonstrated increase in cell number or increased metabolic activity) with the diluted waters. Full strength ozone + chlorine treatment elicited the most unique changes in gene expression. A distinct subset of changes classified by functional effects was shared among diluted ozone + chlorine, 1:10 chlorine and 1:20 chlorinated water-treated hepatocytes, lending support to the theory that these changes were chlorine-mediated and not a result of overt toxicity. There appeared to be a switch from cellular toxicity responses induced by undiluted ozone + chlorine to adaptive responses of the 1:10 and 1:20 diluted ozone + chlorine samples. We surveyed the literature for gene expression changes elicited by haloacetic acids, PPARs, and DEHP and found cellular mechanisms in common with the diluted water samples. We have concluded that DGE can prove useful for bio-monitoring the effects of disinfection processes in hepatocytes.