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 killedat 5, 10, 25, 40 and 55 weeks; additional animals were allowedto live out their natural life span or killed at the terminationof the experiment at 100 weeks. Small nodules of basophiliccells were seen in control animals at 55 weeks. These increasedboth in size and number so that at term nodules were found in17/35 animals examined. Animals given PB showed typical contrilobularhypertrophy. Basophilic nodules were also seen in the treatedanimals and these were similar in form and in number to thoseseen in control animals. The total number of liver nodules seenin animals given PB was, however, greater than the number seenin control animals. The increased nodule burden was a resultof the development of a second nodule type that was first seenin animals killed at 40 weeks. These nodules were formed oflarge epsinophilic cells that had a similar appearence to thehypertrophied cells of the centrilobular region. In contrastthe incidence of carcinoma in PB-treated animals was not increasedover that of the control group.