Analysis of glutathione-dependent enzyme activities in two different rat hepatomas and in normal liver in relation to their role in resistance to oxidative stress.

The importance of some glutathione metabolic pathways was examined in two highly dedifferentiated hepatomas, Yoshida AH-130 and Morris 3924 A hepatomas, and in normal liver in relation to their role against oxidative stress. The cytosol prepared from Yoshida hepatoma cells decreased the peroxidation rate in normal liver microsomes and mitochondria, but this antioxidant property was not displayed by Morris hepatoma. Glutathione peroxidase and glutathione-S-transferases activities were extremely low in both hepatomas; glutathione reductase activity values were about half the normal liver values. The large decrease in glutathione peroxidase and glutathione-S-transferases suggests that in these two tumors only small amounts of GSH can be used in reduction or conjugation reactions, such as the reduction of hydrogen peroxide and lipid hydroperoxides or the conjugation of GSH with the end products of lipoperoxidation, aldehydes or ketones. The hypothesis of a more efficient GSSG reduction in hepatomas, due to the low glutathione peroxidase/glutathione reductase activity ratio, is also discussed. The described changes in glutathione related enzymes do not seem to have any correlation with the protective effect against the lipoperoxidative processes displayed by some tumors since these enzymatic activities were similar in both hepatomas whereas only Yoshida hepatoma showed antioxidant properties.