Phenotypic instability in focal and nodular lesions induced in a short term system in the rat liver

A comparative morphologic, morphometric and enzyme histochemical investigation of lesions induced by short-term application of N-nitrosomorpholine (NNM) and subsequent so-called 'selection pressure' was carried out in order to assess the characteristics of the numbers of induced putative preneoplastic populations and to cast light on reversibility associated with this model. The glycogen storage foci, mixed cell foci and neoplastic nodules observed after 'selection pressure' were in principle similar to those seen after stop experiments, although alterations in morphology and enzyme phenotype of individual cells were usually far more pronounced after short-term induction. It was established that 75% of the lesions were no longer visible 11 weeks after withdrawal of induction stimuli and that a large proportion of these remaining demonstrated heterogeneity in morphological and histochemical markers indicative of reversion to normal phenotype. After a further 10 weeks a slight increase in number of foci associated with decrease in size and enhanced homogeneity in phenotypic markers was established. The behaviour of foci and nodules undergoing reversion was considered with respect to changes in basophilia and glycogen storage and activity of the enzymes glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, glyceraldehyde 3-phosphate dehydrogenase, glycogen phosphorylase and synthase, acid phosphatase and gamma-glutamyl transpeptidase and correlated with location of altered cellular populations within the liver functional acinus.