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RECORD NUMBER: 19 OF 34

Main Title Role of CC1 (sub 4) Biotransformation in the Activation of Hepatocyte Phospholipase C 'In vivo' and 'In vitro'.
Author Coleman, J. B. ; Condie, L. W. ; Lamb, R. G. ;
CORP Author Environmental Protection Agency, Cincinnati, OH. ;Virginia Commonwealth Univ., Richmond.
Publisher c1988
Year Published 1988
Report Number EPA/600/J-88/315;
Stock Number PB89-207286
Additional Subjects Liver ; Toxicity ; In vivo analysis ; In vitro analysis ; Rats ; Laboratory animals ; Reprints ; Carbon tetrachloride ; Phospholipase C ; Biotransformation ; Enzyme activation ; Cytochrome P-450
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Status
NTIS  PB89-207286 Some EPA libraries have a fiche copy filed under the call number shown. 07/26/2022
Collation 15p
Abstract
Rats treated with a single 0.5 ml/kg dose (ip) of CCl4 exhibited a threefold increase in liver microsomal phospholipase C (PLC) activity that was enhanced by phenobarbital and diminished by metyrapone pretreatment, respectively. Hepatocytes and hepatocellular fractions exposed to 0.5 mM CCl4 in vitro also exhibited a rapid rise in PLC activity that was reduced by metyrapone. Metyrapone also reduced the CCl4-related increase in the PLC-mediated reductions in cellular phosphatidylcholine content. The influence of CCl4 biotransformation on the activation of liver cell PLC was assessed in vitro. Covalent binding of CCl4 metabolites to isolated hepatocyte proteins and lipids was linear through 20 min of incubation and then quickly plateaued. Results suggest that chemical metabolites activate PLC in vitro and in vivo. Therefore, the activation of a PLC that degrades membrane phospholipids may represent an important step in the pathogenic scheme of chemical-mediated liver cell necrosis. (Copyright (c) 1988 Academic Press, Inc.)