Phospholipase A2 activation and cell injury in isolated rat hepatocytes exposed to bromotrichloromethane, chloroform, and 1,1-dichloroethylene as compared to effects of carbon tetrachloride.
It was found that the four toxigenic agents, CCl4, CHCl3, CBrCl3, and 1,1-dichloroethylene (vinylidene chloride) all share the property of activating phospholipase A2 (PLA2) of isolated hepatocytes in suspension, as determined over a 60- or 120-min time period. In all cases, PLA2 activation, measured as the appearance of lysophosphatidylethanolamine, preceded the release of lactic dehydrogenase during incubation of the cells at 37 degrees C. It is concluded that for these halogenated hydrocarbons phospholipase A2 activation may be part of the chain of causality leading from initial bioactivation to ultimate cell death.
Glende
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Department of Physiology & Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4970.
Recknagel
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D000818:Animals; D001975:Bromotrichloromethane / Q000633:toxicity*; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002725:Chloroform / Q000633:toxicity*; D004000:Dichloroethylenes / Q000633:toxicity*; D004789:Enzyme Activation / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D011919:Rats, Inbred Strains
D004000:Dichloroethylenes; C029297:vinylidene chloride; D002725:Chloroform; D002251:Carbon Tetrachloride; D007770:L-Lactate Dehydrogenase; D010741:Phospholipases A; D054467:Phospholipases A2; D001975:Bromotrichloromethane