Characterization of Dimethylnitrosamineinduced Focal and Nodular Lesions in the Livers of Newborn Mice

Abstract

Newborn Swiss-Webster mice were given an intraperitoneal injection of 25 μg of dimethylnitrosamine. At weaning they began receiving 0.05% phenobarbital in the drinking water to promote the lesions for the term of the study. Preneoplastic foci and hyperplastic nodules were identified histologically by two markers, resistance to exogenous iron accumulation and an increase in γ-glutamyltranspeptidase activity. AT 8, 12, and 16 weeks of age, livers of affected male mice exhibited 12, 18, and 12 iron-resistant foci/cm2 and 13, 9, and 9 γ-glutamyltranspeptidase-positive foci/cm2, respectively (average for median right and right anterior sublobes). Iron-resistant nodules were first observed at 8 weeks; however, γ-glutamyltranspeptidase-positive nodules were not noted until 12 weeks. In animals that received dimethylnitrosamine but were not placed on phenobarbital, there was an average of 5 foci/cm2 (iron-resistant or γ-glutamyltranspeptidase-positive) at 12 weeks while no nodules were noted. This model could provide a practical short-term in vivo tool for the detection of early sequential cellular alterations produced by initiators, inhibitors, and promoters of carcinogenesis.