Effect of phenobarbital on the gamma-glutamyltranspeptidase activity and the remodeling of nodules induced by the initiation-selection model.

The effect of subsequent administration of phenobarbital on the gamma-glutamyltranspeptidase (GGT) activity and on the remodeling of nodules induced by the Solt-Farber procedure was examined in rats. GGT-nodules were initiated by diethylnitrosamine (DENA) followed by selection with 2-acetylaminofluorene (2AAF) in the diet and a partial hepatectomy (PH). Phenobarbital (500 ppm in the drinking water), administered to rats that were previously treated according to the Solt-Farber procedure, (1) increased the persistence of the GGT-nodules, (2) increased the percentage of the liver occupied by GGT positive cells, (3) increased the area of GGT activity per nodule and (4) increased the incidence of eosinophilic lesions. Subsequent treatment with phenobarbital did not alter the incidence of either GGT-nodules or hepatocellular carcinoma. Thus, phenobarbital increased the GGT activity of nodules induced by the Solt-Farber procedure and slowed both the loss of GGT activity by these nodules and their concurrent remodeling, but had no effect on the occurrence of cancer.