Abstract
When liver microsomes from phenobarbitone-treated rats are incubated with carbon disulfide, a marked loss of cytochrome P-450 is observed only when NADPH is present. By employing 14C- and 25S-labeled CS2, it has been found that in the presence of NADPH labeled sulfur becomes covalently bound to microsomes: The binding of 35S exceeds that of 14C, indicating that sulfur itself becomes bound. A loss of cytochrome P-450 is also seen when parathion, phenylthiourea, or 1-naphthylisothiocyanate is incubated with liver microsomes in the presence of NADPH, whereas the oxygen-containing analogues of these compounds are all inactive. It is concluded that reactive sulfur liberated during the oxidative desulfuration of several chemicals may become bound to cellular components and initiate toxic changes in the liver. This may account not only for the loss of cytochrome P-450 but also for the centrilobular hydropic degeneration seen in vivo.
ACKNOWLEDGMENTS The author would like to thank Mr. A. H. Gibbs and Mr. T. W. Poole for skilled technical assistance.
- Copyright ©, 1974, by Academic Press, Inc.