The effect of pre- and post-treatment with phenobarbital on the extent of gamma-glutamyl transpeptidase positive foci induced in rat liver by N-nitrosomorpholine.

Male Sprague-Dawley rats were treated with a combination of N-nitrosomorpholine (NNM) and phenobarbital and the extent of foci positive for gamma-glutamyl transpeptidase (gamma-GT), as demonstrated histochemically in liver, was quantitated. Phenobarbital (0.05% in the diet) was given either alone, before, or after a 7-week period of treatment with NNM (80 ppm in the drinking water). When given after the carcinogen treatment, phenobarbital enhanced the formation of gamma-GT-positive foci in liver compared with rats treated with NNM alone. No such increase, however, was observed when phenobarbital was administered before treatment with NNM. Phenobarbital alone did not produce any apparent amount of foci in liver. These data suggest that the enhancement of carcinogenic response mediated by phenobarbital as observed under the present experimental conditions is only operative in the presence of pre-existing initiated hepatocytes.