Clonal origin of gamma-glutamyl transpeptidase-positive hepatic lesions induced by initiation-promotion in ornithine carbamoyltransferase mosaic mice.

Since the deficiency of ornithine carbamoyltransferase (OCT) is inherited as an X-linked dominant trait in sparse-fur with abnormal skin and hair (Spf-ash) mice, the livers of heterozygous Spf-ash females show mosaicism in regard to OCT. We induced enzyme-altered foci and nodules, presumptive preneoplastic lesions for hepatocellular carcinomas, in the livers of OCT mosaic mice (Spf-ash x C3H F1), and investigated the clonality of the lesions. Simultaneous histochemical staining for OCT and gamma-glutamyl transpeptidase (GGT) demonstrated that all GGT-positive lesions (ranging in size from 3 cells to a few millimeters in diameter) were either positive or negative for OCT, and no mosaic lesions were detectable. The results indicate that individual enzyme-altered hepatocytic lesions are the result of clonal proliferation.