GLUTATHIONE METABOLISM IN HEPATOMOUS LIVER OF RATS TREATED WITH DIETHYLNITROSAMINE

Glutathione metabolism was studied in rat liver during diethylnitrosam ine (DEN) carcinogenesis. Some studies were also made in foetal rat li ver. Endogenous GSH and non-protein thiols concentrations are increase d in DEN-treated rats when compared to non-treated rats but no differe nces were found in cysteine, total thiols and protein thiols concentra tion. In foetal liver GSH concentration is only 35% of that in DEN-tre ated rat liver. The activities of several enzymes involved in glutathi one metabolism are changed in DEN-treated rats. gamma-Glutamyl transfe rase activity and cysteine formation from GSH by liver homogenates is increased sevenfold. gamma-Glutamylcysteine synthetase activity, initi al rate of [S-35]cysteine incorporation in gamma-glutamylcysteine and initial rate of GSH formation from [S-35]cysteine are increased two-fo ld. Cytosolic GSH S-transferase activity is increased twofold in DEN-t reated rats and so GSH S-conjugates concentration is probably also inc reased. In foetal rat liver gamma-glutamyl transferase activity is abo ut the same but gamma-glutamylcysteine synthetase activity is only 10% of that in DEN-treated rat liver. The increased GSH concentration in DEN-treated rat liver is probably due to the simultaneous increase in the activities of gamma-glutamyl transferase and gamma-glutamylcystein e synthetase. Blood plasma total glutathione is increased 1.4 times in DEN-treated rats, but no differences are found in GSH hepatic arterio venous gradient. This associated with the increased gamma-glutamyl tra nsferase activity suggests that sinusoidal GSH efflux is increased in DEN-treated rats.