| Interactive Toxicity and Stress Protein Expression by Vinylidene Chloride and Monochloroacetate in Precision-Cut Rat Liver Slices Jayanthika Wijeweera, Jay Gandolfi, and Xing Hui Zheng Department of Anesthesiology, University of Arizona, Tucson, Arizona Abstract
Vinylidene chloride (VDC) is a groundwater and drinking water contaminant. Monochloroacetic acid (MCA) is a chlorination by-product of drinking water. Because environmental or occupational exposure to chemicals takes place at low concentrations, a sensitive in vitro system of liver slices was used to examine the interactive toxicity of MCA and VDC. Liver slices from Sprague-Dawley rats were exposed to 100 µM MCA for 1 hr before exposure to 20 or 48 µM VDC and incubated for 1 to 8 hr. MCA+48 µM VDC resulted in a significant leakage of K+ by 4 hr, while MCA+20 µM VDC did not. At 4 hr, MCA+48 µM VDC resulted in centrilobular necrosis. MCA caused a significant depletion of slice glutathione (GSH) at 1 hr, which was maintained up to 3 hr. As reactive VDC metabolites are detoxified by conjugation with GSH, the increase in VDC toxicity by MCA is possibly due to GSH-depleting effects of MCA. Heat shock protein (HSP) 72 was increased 2.5-fold by MCA+20 µM VDC as early as 2 hr, although K+ leakage was not increased. MCA+48 µM VDC resulted in a 3-fold increase in HSP 72 by 2 hr, while there were modest increases in HSPs 60 and 32. Therefore, HSP 72 is an early sensitive indicator of interactive toxicity of nontoxic concentrations of MCA and VDC. This is the first time that micromolar concentrations of these drinking water contaminants were observed to affect cellular homeostasis in the liver. -- Environ Health Perspect 106(Suppl 6) :1319-1323 (1998) . http://ehpnet1.niehs.nih.gov/docs/1998/Suppl-6/1319-1323wijeweera/abstract.html Key words: drinking water contaminants, vinylidene chloride, monochloroacetic acid, interactive hepatotoxicity, stress proteins, glutathione
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