Comparative Study on the Effect of Different Treatment Schedules on Some Carbohydrate Metabolizing Enzyme Activities in Rats During Hepatocarcinogenesis
Phenobarbital (PB) is a well known tumor promoter, which in combination with an initiating drug is able to accelerate the development of γ-glutamyl-transferase (γ-GT)-positive foci and to induce tumor formation after long term feeding1–4. PB is also found to stimulate liver growth1,3,5. The hypolipidaemic drugs nafenopin and clofibrate induce liver tumors when fed to rats or mice6–9. They do not, however, stimulate growth of γ-GT-positive foci3,10,11. Recently we have shown some alterations in carbohydrate metabolizing enzymes in hepatocarcinomas induced with NNM and promoted by long term feeding with phenobarbital or clofibrate12. Pyruvate Kinase (PK) and fructose-1,6-biphosphatase (FBPase) activities were reduced and malic enzyme activity was increased in these rat liver tumors with and without PB or clofibrate feeding. The activity of γ-GT, however, was dependent on the applicated drugs since only PB induced γ-GT-positive hepatocarcinomas. In this study activities of some enzymes were recorded after short term feeding of PB, clofibrate (Clof) or nafenopin (Naf) for 6 and 16 weeks. The results were compared with data obtained from long term application of these compounds for 64 weeks. Pyruvate kinase isoenzyme type L (LPK), malic enzyme (ME) and γ-glutamyltransferase were also investigated by immunohistological and histochemical methods.
KeywordsPyruvate Kinase Malic Enzyme G6PDH Activity Pyruvate Kinase Activity Liver Growth
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