Interactive toxicity and stress protein expression by vinylidene chloride and monochloroacetate in precision-cut rat liver slices.
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 microM MCA for 1 hr before exposure to 20 or 48 microM VDC and incubated for 1 to 8 hr. MCA + 48 microM VDC resulted in a significant leakage of K+ by 4 hr, while MCA+ 20 microM VDC did not. At 4 hr, MCA + 48 microM 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 microM VDC as early as 2 hr, although K+ leakage was not increased. MCA + 48 microM 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.
Wijeweera
J
J
Department of Anesthesiology, University of Arizona, Tucson, USA.
Gandolfi
J
J
Zheng
X H
XH
D000085:Acetates / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D015153:Blotting, Western; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology; D004000:Dichloroethylenes / Q000378:metabolism / Q000633:toxicity*; D004347:Drug Interactions; D005978:Glutathione / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014874:Water Pollutants, Chemical / Q000633:toxicity
D000085:Acetates; D004000:Dichloroethylenes; D006360:Heat-Shock Proteins; D014874:Water Pollutants, Chemical; C029297:vinylidene chloride; C006972:chloroacetic acid; D005978:Glutathione