Potentiating effects of chlorinated hydrocarbons on carbon tetrachloride toxicity in isolated rat hepatocytes and plasma membranes.
A number of chemicals are known to potentiate the hepatotoxicity of carbon tetrachloride. The halocarbon trichloroethylene was shown in a previous study to enhance both carbon tetrachloride-induced toxicity and lipid peroxidation in isolated hepatocytes. In this study three other chlorocarbons have been investigated in order to determine whether this interaction was peculiar to trichloroethylene or common to chlorinated solvents. Hepatocyte suspensions were exposed to carbon tetrachloride at subthreshold levels of toxicity and various concentrations of 1,1,1-trichloroethane, tetrachloroethylene, and chloroform over an eightfold concentration range. Plasma membrane preparations were exposed to tetrachloroethylene and carbon tetrachloride and effects on Mg(2+)- and Na(+)-K(+)-ATPase activities determined. None of the treatments alone caused statistically significant toxicity. Combined treatments resulted in toxicity as demonstrated by potassium ion, alanine aminotransferase, and lactate dehydrogenase leakage from the cells on coincubation of carbon tetrachloride with each of the other halocarbons studied. Only tetrachloroethylene and chloroform were found to potentiate lipid peroxidation, however. In liver plasma membranes no changes in Na(+)-K(+)-ATPase were observed with any of the treatments and only the highest dose of tetrachloroethylene was able to inhibit Mg(2+)-ATPase activity. There was no increase in this inhibition on coincubation with carbon tetrachloride, which does not support involvement of ATPases in combined halocarbon toxicity. In conclusion, the data suggest a mechanism of action common to this class of chemical although its specific nature remains to be established.
Kefalas
V
V
National Institute of Occupational Health and Safety, University of Sydney, New South Wales, Australia.
Stacey
N H
NH
D000251:Adenosine Triphosphatases / Q000187:drug effects; D000410:Alanine Transaminase / Q000187:drug effects; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D002470:Cell Survival / Q000187:drug effects; D002725:Chloroform / Q000633:toxicity; D004357:Drug Synergism; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013750:Tetrachloroethylene / Q000633:toxicity; D014240:Trichloroethanes / Q000633:toxicity
D006843:Hydrocarbons, Chlorinated; D014240:Trichloroethanes; C024566:1,1,1-trichloroethane; D002725:Chloroform; D002251:Carbon Tetrachloride; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase; D000251:Adenosine Triphosphatases; D011188:Potassium; D013750:Tetrachloroethylene