The phenotypic stability of altered hepatic foci: Effect of the shortterm withdrawal of phenobarbital and of the long-term feeding of purified diets after the withdrawal of phenobarbital

The effects of the short-term withdrawal of phenobarbital (PB) and of the feeding of purified diets during the long-term withdrawal of dietary PB on the stability of altered hepatic foci (AHF) were studied. In both experiments female CD rats initially received an intragastric dose of diethylnitrosamine (10 mg/kg) 20 h after being subjected to partial hepatectomy. In the short-term study rats were fed 0.05% PB in a cerealbased diet for 6 months; at this time half of the rats were killed, whereas the other half were withdrawn from PB for 10 days before sacrifice. Withdrawing PB for 10 days resulted in a decrease in the number and volume of AHF, particularly those which stained positively for gamma-glutamyltranspeptidase (GGT). In the long-term experiment rats were fed 0.05% phenobarbital in a cereal-based diet for 3 months; they were then withdrawn from the cereal-based diet containing PB and fed either a low-fat or a high-fat purified diet without PB for 8 months. At this time the number and volume of AHF were much less than that seen at the time of PB withdrawal. In addition, the distribution of phenotypes was altered: the percentage of foci containing GGT as a marker decreased dramatically. These results indicate that certain phenotypic characteristics of AHF, specifically their observable number and total volume, rapidly decrease after the withdrawal of PB from rats fed a cereal-based diet and that the feeding of purified diets after such PB withdrawal does not result in the reappearance of AHF. These studies suggest that the phenotype, volume and observable number of AHF may change in the absence of PB as compared with its presence in the diet and that some cereal-based diets may contain unspecified agents which 'stabilize' or enhance the phenotypic appearance of AHF.