Glutathione synthesis and degradation in fetal and adult rat liver and Novikoff hepatoma
Wirth, P.J.; Thorgeirsson, S.S.
Cancer Research 38(9): 2861-2865
1978
ISSN/ISBN: 0008-5472 PMID: 28177 Document Number: 136981
The in vitro activities of the 3 main enzymes involved in the synthesis and degradation of glutathione [GSH] (.gamma.-glutamylcysteine synthetase, glutathione synthetase and .gamma.-glutamyltranspeptidase) were studied in normal adult rat liver, fetal rat liver and transplantable, rapidly growing, undifferentiated Novikoff hepatoma. The total GSH content in the Novikoff hepatoma and fetal rat liver was similar, and both tissues had significantly (P < 0.05) lower GSH content than adult rat liver. GSH was rapidly depleted in vivo following i.p. administration of diethyl maleate to male Sprague-Dawley rats with and without transplanted Novikoff hepatomas. Liver GSH levels in adult control rats were rapidly decreased to 15% of control levels 30 min after diethyl maleate administration and remained maximally depleted for 4 h after which they began to rise, rapidly returning to normal values at 6 h and 200% of normal at 24 h. GSH levels in transplanted tumors were maximally depleted (23% of normal) after 4 h and showed a slower rate of synthesis reaching normal levels only after 24 h. GSH levels in fetal rat liver were depleted to 25% of control levels after 3 h, rose to control values after 9 h, but, unlike levels in adult rat liver and levels in the Novikoff hepatoma, the overshoot phenomenon for the resynthesis of GSH was not observed. The in vitro activity of .gamma.-glutamyltranspeptidase in the Novikoff hepatoma and fetal liver was markedly increased (50- and 16-fold, resplectively) over the transpeptidase activity in adult rat liver. In vitro .gamma.-glutamylcysteine synthetase activity in adult control liver was 3-4 times greater than the synthetase activity in fetal liver greater than the synthetase activity in fetal liver or Novikoff hepatoma. The synthesis of GSH, was 14 times greater in adult liver than in Novikoff hepatoma and 3 times greater than in fetal liver. GSH (5 mM) inhibited the activity of .gamma.-glutamylcysteine synthetase to the same degree in adult liver, fetal liver and Novikoff hepatoma, suggesting that the synthetase has similar enzymatic characteristics in all tissues.