||Role of CC1 (sub 4) Biotransformation in the Activation of Hepatocyte Phospholipase C 'In vivo' and 'In vitro'.
Coleman, J. B. ;
Condie, L. W. ;
Lamb, R. G. ;
||Environmental Protection Agency, Cincinnati, OH. ;Virginia Commonwealth Univ., Richmond.
In vivo analysis ;
In vitro analysis ;
Laboratory animals ;
Carbon tetrachloride ;
Phospholipase C ;
Enzyme activation ;
||Some EPA libraries have a fiche copy filed under the call number shown.
||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.)
||Pub. in Toxicology and Applied Pharmacology, v95 n2 p208-219 Sep 88. See also PB89-207278. Prepared in cooperation with Virginia Commonwealth Univ., Richmond.
|NTIS Title Notes
||Reprint: Role of CC1 (sub 4) Biotransformation in the Activation of Hepatocyte Phospholipase C 'In vivo' and 'In vitro'.
||PC A03/MF A01