The histology and development of hepatic nodules and carcinoma in C3H/He and C57BL/6 mice following chronic phenobarbitone administration.

Male C3H/He and C57BL/6 mice were given diets containing sodium phenobarbitone (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 killed 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 found in 1/5 control C3H/He mice at 30 wk; these nodules increased in number 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 mice until 80 wk, when they were found in 4% of mice. PB treatment markedly increased the number of hepatic nodules in both strains of mice. The additional nodule burden was due to the development of a second nodule type formed of large cells with a predominantly eosinophilic cytoplasm. 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 not increased by PB treatment in either strain. It is concluded that both strains of mice behave in a qualitively similar way to PB administration, although they show considerable quantitative differences in terms of the time and number of nodules that develop. Furthermore, the increased nodule numbers associated with PB treatment were not accompanied by an increase in the number of carcinomas.