Abstract
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.
Keywords: Spf‐ash mice, Ornithine carbamoyltransferase, Mosaicism, Clonal proliferation
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References
- 1. ) Fialkow , P. J.Clonal origin of human tumors . Biochim. Biophys. Acta , 458 , 283 – 321 ( 1976. ). [DOI] [PubMed] [Google Scholar]
- 2. ) Weinberg , W. C. , Berkwits , L. and Iannaccone , P. M.The clonal nature of carcinogen induced foci of inappropriate expression of γ‐glutamyl transpeptidase in rat liver . Carcinogenesis , 8 , 565 – 570 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 3. ) Reddy , A. L. and Fialkow , P. J.Papillomas induced by initiation‐promotion differ from those induced by carcinogen alone . Nature , 304 , 69 – 71 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 4. ) Taguchi , T. , Yokoyama , M. and Kitamura , Y.Intraclonal conversion from papilloma to carcinoma in the skin of Pgk‐la/Pgk‐lb mice treated by a complete carcinogenesis process or by an initiation‐promotion regimen . Cancer Res. , 44 , 3779 – 3782 ( 1984. ). [PubMed] [Google Scholar]
- 5. ) Rabes , H. M. , Bücher , Th. , Hartmann , A. , Linke , I. and Dünnwald , M.Clonal growth of carcinogen‐induced enzyme‐deficient preneoplastic cell populations in mouse liver . Cancer Res. , 42 , 3220 – 3227 ( 1982. ). [PubMed] [Google Scholar]
- 6. ) Howell , S. , Wareham , K. A. and Williams , E. D.Clonal origin of mouse liver cell tumors . Am. J. Pathol. , 121 , 426 – 432 ( 1985. ). [PMC free article] [PubMed] [Google Scholar]
- 7. ) Lyon , M. F.Gene action in the X‐chromosome of the mouse . Nature , 190 , 372 – 373 ( 1961. ). [DOI] [PubMed] [Google Scholar]
- 8. ) Mizutani , A.Cytochemical demonstration of ornithine carbamoyltransferase activity in liver mitochondria of rat and mouse . J. Histochem. Cytochem. , 16 , 172 – 180 ( 1968. ). [DOI] [PubMed] [Google Scholar]
- 9. ) Doolittle , D. P. , Hulbert , L. L. and Cordy , C.A new allele of the sparse fur gene in the mouse . J. Hered. , 65 , 194 ( 1974. ). [DOI] [PubMed] [Google Scholar]
- 10. ) Rutenburg , A. M. , Kim , H. , Fischbein , J. W. , Hanker , J. S. , Wasserkurg , H. L. and Seligman , A. M.Histochemical and ultrastructural demonstration of γ‐glutamyl transpeptidase activity . J. Histochem. Cytochem. , 17 , 517 – 526 ( 1969. ). [DOI] [PubMed] [Google Scholar]
- 11. ) Jalanko , H. and Ruoslahti , E.Differential expression of α‐fetoprotein and γ‐glutamyl transpeptidase in chemical and spontaneous hepatocarcinogenesis . Cancer Res. , 39 , 3495 – 3501 ( 1979. ). [PubMed] [Google Scholar]