Abstract
Liver tissues of LEG rats, which develop fulminant hepatitis and hepatocellular carcinoma (hepatoma), were examined by Northern blot analysis using a cDNA probe of rat placental glutathione S‐transferase (GST‐P). GST‐P gene expression was observed not only during hepatocarcinogenesis but also in fulminant hepatitis before development of chronic hepatitis and hepatoma in LEC rats. Cholangiofibrosis in LEC rats also showed high GST‐P expression. A transplantable cell line derived from spontaneous LEC hepatoma exhibited a remarkably high expression. By contrast, very weak expression was observed in the livers of young LEC rats before development of hepatitis and control strain rats. Thus, spontaneous hepatic lesions in LEC rats may provide a new clue to elucidate the mechanism of GST‐P gene expression.
Keywords: LEC rats, Hereditary hepatitis, Spontaneous hepatocarcinogenesis, Placental glutathione S‐transferase, Gene expression
Full Text
The Full Text of this article is available as a PDF (218.0 KB).
REFERENCES
- 1. ) Sasaki , M. , Yoshida , M. C. , Kagami , K. , Takeichi , N. , Kobayashi , H. , Dempo , K , and Mori , M.Spontaneous hepatitis in an inbred strain of Long‐Evans rats . Rat News Lett. , 14 , 4 – 6 ( 1985. ). [Google Scholar]
- 2. ) Yoshida , M. C. , Masuda , R. , Sasaki , M. , Takeichi , N. , Kobayashi , H. , Dempo , K , and Mori , M.New mutation causing hereditary hepatitis in the laboratory rat . J. Hered. , 78 , 361 – 365 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 3. ) Masuda , R. , Yoshida , M. C. , Sasaki , M. , Dempo , K. and Mori , M.Hereditary hepatitis of LEC rats is controlled by a single autosomal recessive gene . Lab. Anim. , 22 , 166 – 169 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 4. ) Masuda , R. , Yoshida , M. C. , Sasaki , M. , Dempo , K. and Mori , M.High susceptibility to hepatocellular carcinoma development in LEC rats with hereditary hepatitis . Jpn. J. Cancer Res. , 79 , 828 – 835 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. ) Kitahara , A. , Satoh , K. , Nishimura , K. , Ishikawa , T. , Ruike , K. , Sato , K. , Tsuda , H. and Ito , N.Changes in molecular forms of rat hepatic glutathione S‐transferase during chemical hepatocarcinogenesis . Cancer Res. , 44 , 2698 – 2703 ( 1984. ). [PubMed] [Google Scholar]
- 6. ) Sato , K. , Kitahara , A. , Satoh , K. , Ishikawa , T. , Tatematsu , M. and Ito , N.The placental form of glutathione S‐transferase as a new marker protein for preneoplasia in rat chemical hepatocarcinogenesis . Gann , 75 , 199 – 202 ( 1984. ). [PubMed] [Google Scholar]
- 7. ) Satoh , K. , Kitahara , A. , Soma , Y. , Inaba , Y. , Hatayama , I. and Sato , K.Purification, induction, and distribution of placental glutathione transferase: a new marker enzyme for preneoplastic cells in the rat chemical hepatocarcinogenesis . Proc. Natl. Acad. Sci. USA , 82 , 3964 – 3968 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. ) Sugioka , Y. , Fujii‐Kuriyama , Y. , Kitagawa , T. and Muramatsu , M.Changes in polypeptide pattern of rat liver cells during chemical hepatocarcinogenesis . Cancer Res. , 45 , 365 – 378 ( 1985. ). [PubMed] [Google Scholar]
- 9. ) Sato , K.Glutathione S‐transferases and hepatocarcinogenesis . Jpn. J. Cancer Res. , 79 , 556 – 572 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. ) Oyamada , M. , Dempo , K. , Fujimoto , Y. , Takahashi , H. , Satoh , M. I. , Mori , M. , Masuda , R. , Yoshida , M. C. , Satoh , K. and Sato , K.Spontaneous occurrence of placental glutathione S‐transferase‐positive foci in the livers of LEC rats . Jpn. J. Cancer Res. , 79 , 5 – 8 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. ) Masuda , R. , Yoshida , M. C. , Sasaki , M. , Dempo , K. and Mori , M.A transplantable cell line derived from spontaneous hepatocellular carcinoma of the hereditary hepatitis LEC rat . Jpn. J. Cancer Res. , 79 , 250 – 254 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. ) Glišin , V. , Crkvenjakov , R. and Byus , C.Ribonucleic acid isolated by cesium chloride centrifugation . Biochemistry , 13 , 2633 – 2637 ( 1974. ). [DOI] [PubMed] [Google Scholar]
- 13. ) Maniatis , T. , Fritsch , E. F. and Sambrook , J.Extraction, purification, and analysis of mRNA from eukaryotic cells . In“Molecular Cloning, a Laboratory Manual ,” pp. 187 – 209 ( 1982. ). Cold Spring Harbor Laboratory; , New York ). [Google Scholar]
- 14. ) Sugioka , Y. , Kano , T. , Okuda , A. , Sakai , M. , Kitagawa , T. and Muramatsu , M.Cloning and the nucleotide sequence of rat glutathione S‐transferase P cDNA . Nucleic Acids Res. , 13 , 6049 – 6057 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. ) Moore , M. A. , Fukushima , S. , Ichihara , A. , Sato , K. and Ito , N.Intestinal metaplasia and altered enzyme expression in propylnitrosamine‐induced Syrian hamster cholangiocelhilar and gallbladder lesions . Virchows Arch. (Cell Pathol.) , 51 , 29 – 38 ( 1986. ). [DOI] [PubMed] [Google Scholar]