Record Display for the EPA National Library Catalog


Main Title Influence of CC1 (sub 4) Biotransformation on the Activation of Rat Liver Phospholipase C '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-88/314;
Stock Number PB89-207278
Additional Subjects Liver ; Toxicity ; In vitro analysis ; Metabolism ; Rats ; Laboratory animals ; Reprints ; Carbon tetrachloride ; Phospholipase C ; Enzyme activation ; Biotransformation
Library Call Number Additional Info Location Last
NTIS  PB89-207278 Some EPA libraries have a fiche copy filed under the call number shown. 07/26/2022
Collation 10p
Carbon tetrachloride (CCl4) biotransformation and covalent binding was measured in 1000g liver fractions by determining the amount of CCl4 metabolites covalently bound to proteins and lipids at various (5-60 min) incubation times. Reactive intermediate binding to proteins and phospholipids peaked at 20 min, whereas CCl4 metabolites associated with neutral lipids (primarily diacylglycerol) were initially low (0-15 min) and then gradually increased from 20-60 min. The rise in labeled diacylglycerol was associated with a decrease in phospholipids containing covalently bound CCl4 metabolites, since CCl4 bioactivation increased phospholipase C (PLC) activity three- to fourfold. In contrast, when CCl4 bioactivation is absent, 0.5mm CCl4 has little effect on PLC activity. PLC activation by high doses of CCl4 occurs by bioactivation-independent mechanisms. Therefore, there are two components of CCl4-induced PLC activation. Under both conditions, the activation of PLC may be a key event in CCl4 hepatotoxicity since PLC disrupts the functional and structural integrity of membranes by degrading membrane phospholipids. (Copyright (c) 1988 Academic Press, Inc.)