Effect of chronic phenobarbital administration on the gamma-glutamyl transpeptidase activity of hyperplastic liver lesions induced in rats by the Solt/Farber initiation: selection process of hepatocacinogenesis

A chronic 8 to 11 week administration of the hepatic tumor promoterphenobarbital (0.05% in drinking water) to rats previously subjectedto the initiation:selection process of Solt and Farber was foundto further increase the gamma-glutamyl transpeptidase activityof individual hyperplastic liver nodules of 4.0–10.0 mmin diameter over comparably sized nodules form control livers.Those rats which received 11 weeks of the chronic phenobarbitaltreatment also showed a significant increase in their liverwet weights. In addition, random tissue samples of non-nodularliver taken from the 11 week phenobarbital-treated rats exhibiteda gamma-glutamyl transpeptidase mean specific activity whichwas {small tilde}3 times higher than that of control non-nodularliver samples. In contrast, there was a 1.9-fold increase inthe mean % gamma-glutamyl transpeptidase-positive area (cm²),as determined histochemically, in cryostat sections made fromnon-nodular samples of the 11 week phenobarbital-treated ratswhen compared with that of control liver sections. Interruptionof the chronic phenobarbital administration at 8 weeks followedby 3 weeks of control treatment resulted in a reversal of thegammaglutamyl transpeptidase activity response shown by thehyperplastic liver nodules and non-nodular liver tissue samples.Thus, phenobarbital can quantitatively modulate gamma-glutamyltranspeptidase activity in carcinogeninduced hyperplastic liverlesions in the rat during the early stages of hepatocarcinogenesis.