Sustained induction of hepatic xenobiotic metabolising enzyme activities by phenobarbitone in C3H/He mice: relevance to nodule formation.

Phenobarbitone (PB) was administered to male C3H/He mice at a dose of 85 mg/kg/day in a semisynthetic diet for up to 90 weeks. Throughout the treatment period a sustained induction of a number of parameters of hepatic Phase I and Phase II xenobiotic metabolism was observed. Histological examination revealed hypertrophy of the centrilobular cells of the liver lobule in PB treated mice and after 25 weeks small basophilic nodules were found in control and PB treated animals. In addition eosinophilic nodules, which were often large, developed in PB treated mice. Xenobiotic metabolising enzyme activities in large excised nodules after 70 or 90 weeks of PB treatment were either similar to or greater than those present in surrounding host tissue. Both phenobarbitone- and polycyclic hydrocarbon-type mixed function oxidase enzyme activities were induced in large nodules. In conclusion, PB produced a sustained induction of xenobiotic metabolising enzymes both in host tissue and in large eosinophilic nodules. The formation of these nodules in C3H/He mice was thus not associated with any failure of induction of hepatic xenobiotic metabolism.