Abstract
Properties of hyperplastic hepatic nodules, presumptive preneoplastic lesions of hepatocellular carcinomas, were investigated in mosaic rodents of which livers comprise two genetically-different lineages of cells. In the first experiment, we explored the monoclonality of hyperplastic nodules induced by DEN and phenobarbital in female C3H×spf-ash F1 mice of which livers are composed of hepatocytes with and without ornithine carbamyl transferase (OCT) activity. Simultaneous staining for OCT and γ-glutamyltranspeptidase activities demonstrated that the nodules were composed entirely of one or the other of 2 lineages, representing their monoclonality. The second experiment was carried out to investigate the phenotypic reversion of early hyperplastic nodules by using transplantation system between analbuminemic rats (NAR) and SD×NAR F1 rats. Hyperplastic nodule cells isolated from NAR were transplanted into the liver of SD×NAR F1 rats of which livers are positive for albumin. In those recipient mosaic rats, hyperplastic nodules were virtually negative for albumin and the surrounding nonhyperplastic nodule cells were positive. It became clear that, although hyperplastic nodules express biochemical markers during administration of promoting stimuli, they revert to become phenotypically normal after removal of the stimuli.
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