THE HISTOLOGY AND DEVELOPMENT OF HEPATIC NODULES AND CARCINOMA IN C3HHE AND C57BL/6 MICE FOLLOWING CHRONIC PHENOBARBITONE ADMINISTRATION/

Male C3H/He and C57BL/6 mice were given diets containing sodium phenob arbitone (PB) to allow a daily intake of 85 mg/kg. Control and treated animals were killed at 5, 30, 40, 60, and 80 wk. Other mice were kill ed in extremis or at the end of the respective experiments: 91 wk for C3H/He and 100 wk for the C57BL/6 animals. A basophilic nodule was fou nd in 115 control C3H/He mice at 30 wk; these nodules increased in num ber with time so that nodules of this type were found in approximately 70% of animals by 91 wk. Nodules were not found in control C57BL/6 mi ce until 80 wk, when they were found in 4% of mice. PB treatment marke dly increased the number of hepatic nodules in both strains of mice. T he additional nodule burden was due to the development of a second nod ule type formed of large cells with a predominantly eosinophilic cytop lasm. C3H/He animals given PB for 60 wk and then returned to a control diet bore fewer nodules at 91 wk than treated mice killed at 60 or 91 wk. The cumulative incidence of carcinoma in control C3H/He and C57BL /6 mice was 28 and 4%, respectively. The incidence of carcinoma was no t increased by PB treatment in either strain. It is concluded that bot h strains of mice behave in a qualitively similar way to PB administra tion, although they show considerable quantitative differences in term s of the time and number of nodules that develop. Furthermore, the inc reased nodule numbers associated with PB treatment were not accompanie d by an increase in the number of carcinomas.