Utilization of circulating glutathione by nodular and cancerous intact rat liver

The relationship of the rate of extraction of circulating glutathione (GSH) to the level of activity of gamma-glutamyltransferase (GGT) of hepatocytes of nodular and of cancer-bearing livers was studied in rats perfused in situ via the portal vein. Fischer adult male rats with many nodules (10 rats) or few (nine rats) liver nodules and four rats with hepatomas were compared as to their ability to remove GSH (10 microM) from the perfusate. The rate of extraction of infused GSH was directly proportional to the numbers of GGT(+)-hepatocytes in the liver tissue, inhibitable completely by adding the GGT inhibitor serine borate at 6-8 mM in the perfusate, and significantly enhanced in all rats by adding the gamma-glutamyl acceptor glycyl-glycine to the perfusate. These results suggest that nodules and cancers are able to remove GSH much more efficiently from the circulation than the surrounding liver tissue and that their enhanced GSH utilization is directly dependent on their GGT activity, which is present at much higher levels than in the surrounding tissues. The increases in GGT activity in nodule hepatocytes and enhanced ability to utilize GSH could be critical factors in the response to resistance selection of chemical hepatocarcinogenesis.