The histology and development of hepatic nodules in C3H/He mice following chronic administration of phenobarbitone.

Male C3H/He mice were given 0 (control) or 85 mg/kg/day phenobarbitone (PB). Groups of five control and five treated animals were killed at 5, 10, 25, 40 and 55 weeks; additional animals were allowed to live out their natural life span or killed at the termination of the experiment at 100 weeks. Small nodules of basophilic cells were seen in control animals at 55 weeks. These increased both in size and number so that at term nodules were found in 17/35 animals examined. Animals given PB showed typical centrilobular hypertrophy. Basophilic nodules were also seen in the treated animals and these were similar in form and in number to those seen in control animals. The total number of liver nodules seen in animals given PB was, however, greater than the number seen in control animals. The increased nodule burden was a result of the development of a second nodule type that was first seen in animals killed at 40 weeks. These nodules were formed of large eosinophilic cells that had a similar appearance to the hypertrophied cells of the centrilobular region. In contrast the incidence of carcinoma in PB-treated animals was not increased over that of the control group.