CLONAL ORIGIN OF γ‐GLUTAMYL TRANSPEPTIDASE‐POSITIVE HEPATIC LESIONS INDUCED BY INITIATION‐PROMOTION IN ORNITHINE CARBAMOYLTRANSFERASE MOSAIC MICE

Since the deficiency of ornithine carbamoyl‐transferase (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 × C3H F1), and investigated the clonality of the lesions. Simultaneous histochemical staining for OCT and γ‐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.