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 hepatocarcinogenesis.
A chronic 8 to 11 week administration of the hepatic tumor promoter phenobarbital (0.05% in drinking water) to rats previously subjected to the initiation:selection process of Solt and Farber was found to further increase the gamma-glutamyl transpeptidase activity of individual hyperplastic liver nodules of 4.0-10.0 mm in diameter over comparably sized nodules from control livers. Those rats which received 11 weeks of the chronic phenobarbital treatment also showed a significant increase in their liver wet weights. In addition, random tissue samples of non-nodular liver taken from the 11 week phenobarbital-treated rats exhibited a gamma-glutamyl transpeptidase mean specific activity which was approximately 3 times higher than that of control non-nodular liver samples. In contrast, there was a 1.5-fold increase in the mean % gamma-glutamyl transpeptidase-positive area (cm2), as determined histochemically, in cryostat sections made from non-nodular samples of the 11 week phenobarbital-treated rats when compared with that of control liver sections. Interruption of the chronic phenobarbital administration at 8 weeks followed by 3 weeks of control treatment resulted in a reversal of the gamma-glutamyl transpeptidase activity response shown by the hyperplastic liver nodules and non-nodular liver tissue samples. Thus, phenobarbital can quantitatively modulate gamma-glutamyl transpeptidase activity in carcinogen-induced hyperplastic liver lesions in the rat during the early stages of hepatocarcinogenesis.
D000818:Animals; D006965:Hyperplasia; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000201:enzymology; D008297:Male; D010634:Phenobarbital / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
D005723:gamma-Glutamyltransferase; D010634:Phenobarbital