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The LEC Rat pp 54-66 | Cite as

High Susceptibility to Spontaneous Development of Hepatocellular Carcinoma in LEC Rats

  • Ryuichi Masuda
  • Michihiro C. Yoshida
  • Motomichi Sasaki
  • Kimimaro Dempo
  • Michio Mori

Abstract

Spontaneous hepatitis was first found in the LEC strain rat, which had been maintained conventionally at the Center for Experimental Plants and Animals, Hokkaido University [1]. The hepatitis appears suddenly in LEC rats at about 4 months after birth, and leads to a high mortality [2]. Characteristics of the disease are similar to those of fulminant hepatitis in humans, showing bilirubinuria, hyperbilirubinemia (frequently severe jaundice), subcutaneous bleeding, loss of body weight, increased levels of serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and alkaline Phosphatase, and single-cell necrosis or spotty necrosis of liver tissues with faint inflammatory cell response. Genetic analysis by crossing tests indicated that the disease has an autosomal recessive mode of inheritance, being ruled by a single gene designated hts (symbol for hepatitis) [3]. Many rats died of submassive necrosis in liver tissues within 1 week after the onset of hepatitis. The remaining animals survived with chronic hepatitis more than 1 year and developed preneoplastic and neoplastic lesions of the liver [2]. Electron microscopic analysis failed to reveal any viral particles in the affected liver, and intraperitoneal injections of liver homogenates of jaundiced rats did not induce hepatitis in neonatal rats of another strain [2], although viral hepatitis has been reported to be associated with hepatocarcinogenesis in humans [4, 5], woodchucks [6], ground squirrels [7] and ducks [8]. Although the cause of hepatitis in LEC rats is different from that of viral hepatitis in the other cases, regenerative stimuli caused by hepatitis may promote development of liver tumors in all cases. In this report, the natural history of spontaneous hepatic lesions in LEC rats are described with regard to the anatomical and histopathological aspects. Furthermore, establishment and characterization of a hepatocellular carcinoma (hepatoma) cell line obtained from an LEC rat are reported.

Keywords

Ground Squirrel Neoplastic Lesion Fulminant Hepatitis Primary Hepatoma Serum Glutamic Oxaloacetic Transaminase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Sasaki M, Yoshida MC, Kagami K, Takeichi N, Kobayashi H, Dempo K, Mori M (1985) Spontaneous hepatitis in an inbred strain of Long-Evans rats. Rat News Lett 14:4–6.Google Scholar
  2. 2.
    Yoshida MC, Masuda R, Sasaki M, Takeichi N, Kobayashi H, Dempo K, Mori M (1987) New mutation causing hereditary hepatitis in the laboratory rat. J Hered 78:361–365.PubMedGoogle Scholar
  3. 3.
    Masuda R, Yoshida MC, Sasaki M, Dempo K, Mori M (1988) Hereditary hepatitis of LEC rats is controlled by a single autosomal recessive gene. Lab Anim 22:166–169.PubMedCrossRefGoogle Scholar
  4. 4.
    Popper H, Gerber MA, Thung SN (1982) The relation of hepatocellular carcinoma to infection with hepatitis B and related viruses in man and animals. Hepatology (Suppl) 2:1S–9S.Google Scholar
  5. 5.
    Thiollais P, Pourcel C, Dejean A (1985) The hepatitis B virus. Nature 317: 489–495.CrossRefGoogle Scholar
  6. 6.
    Summers J, Smolec MJ, Snyder R (1978) A virus similar to human hepatitis B virus associated with hepatitis and hepatoma in woodchucks. Proc Natl Acad Sci USA 75:4533–4537.PubMedCrossRefGoogle Scholar
  7. 7.
    Marion PL, Davelaar MJV, Knight SS, Salazar FH, Garcia G, Popper H, Robinson WS (1986) Hepatocellular carcinoma in ground squirrels persistently infected with ground squirrel hepatitis virus. Proc Natl Acad Sci USA 83:4543–4546.PubMedCrossRefGoogle Scholar
  8. 8.
    Omata M, Uchiumi K, Ito Y, Yokosuka O, Mori J, Terao K, Wei-Fa Y, O’Connell AP, London WT, Okuda K (1983) Duck hepatitis B virus and liver diseases. Gastroenterology 85:260–267.PubMedGoogle Scholar
  9. 9.
    Masuda R, Yoshida MC, Sasaki M, Dempo K, Mori M (1988) High susceptibility to hepatocellular carcinoma development in LEC rats with hereditary hepatitis. Jpn J Cancer Res 79:828–835.PubMedCrossRefGoogle Scholar
  10. 10.
    Masuda R, Yoshida MC, Sasaki M, Dempo K, Mori M (1988) A transplantable cell line derived from spontaneous hepatocellular carcinoma of the hereditary hepatitis LEC rat. Jpn J Cancer Res 79:250–254.PubMedCrossRefGoogle Scholar
  11. 11.
    Kobayashi K, Fukuoka K, Matsushita F, Morimoto H, Hinoue Y, Honjo H, Tanaka N, Sugimoto T, Kato Y, Hattori N, Ueda S, Kato S (1983) Transplantation of woodchuck hepatocellular carcinoma in nude mice. Hepatology 3: 663–666.PubMedCrossRefGoogle Scholar
  12. 12.
    Unoura M, Kobayashi K, Fukuoka K, Matsushita F, Morimoto H, Oshima T, Kaneko S, Hattori N, Murakami S, Yoshikawa H (1985) Establishment of a cell line from a woodchuck hepatocellular carcinoma. Hepatology 5:1106–1111.PubMedCrossRefGoogle Scholar
  13. 13.
    Abe K, Kurata T, Yamada K, Okumura H, Shikata T (1988) Establishment and characterization of a woodchuck hepatocellular carcinoma cell line (WH44KA). Jpn J Cancer Res 79:342–349.PubMedCrossRefGoogle Scholar
  14. 14.
    Ohnishi S, Aoyama H, Shiga J, Itai Y, Moriyama T, Ishikawa T, Sasaki N, Yamamoto K, Koshimizu K, Kaneko S, Murakami S, Hattori N, Imawari M (1988) Establishment of a new cell line from a woodchuck hepatocellular carcinoma. Hepatology 8:104–107.PubMedCrossRefGoogle Scholar
  15. 15.
    Squire RA, Levitt MH (1975) Report of a workshop on classification of specific hepatocellular lesions in rats. Cancer Res 35:3214–3223.PubMedGoogle Scholar
  16. 16.
    Ward JM (1981) Morphology of foci of altered hepatocytes and naturallyoccurring hepatocellular tumors in F344 rats. Virchows Arch [A] 390:339–345.CrossRefGoogle Scholar
  17. 17.
    Maekawa A, Kurokawa Y, Takahashi M, Kokubo T, Ogiu T, Onodera H, Tanigawa H, Ohno Y, Furukawa F, Hayashi Y (1983) Spontaneous tumors in F-344/DuCrj rats. Jpn J Cancer Res 74:365–372.Google Scholar
  18. 18.
    Solleveld HA, Haseman JK, McConnell EE (1984) Natural history of body weight gain, survival, and neoplasia in the F344 rat. J Natl Cancer Inst 72: 929–940.PubMedGoogle Scholar
  19. 19.
    Pollard M, Luckert PH (1979) Spontaneous liver tumors in aged germfree Wistar rats. Lab Anim Sci 29:74–77.PubMedGoogle Scholar
  20. 20.
    Heston WE, Vlahakis G (1968) C3H-Avy — A high hepatoma and high mammary tumor strain of mice. J Natl Cancer Inst 40:1161–1166.PubMedGoogle Scholar
  21. 21.
    Ward JM, Vlahakis G (1978) Evaluation of hepatocellular neoplasms in mice. J Natl Cancer Inst 61:807–811.PubMedGoogle Scholar
  22. 22.
    Oyamada M, Dempo K, Fujimoto Y, Takahashi H, Satoh MI, Mori M, Masuda R, Yoshida MC, Satoh K, Sato K (1988) Spontaneous occurrence of placental glutathione S-transferase-positive foci in the livers of LEC rats. Jpn J Cancer Res 79:5–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Reuber MD (1969) Influence of hormones on N-2-fluorenyldiacetamide-induced hyperplastic hepatic nodules in rats. J Natl Cancer Inst 43:445–451.PubMedGoogle Scholar
  24. 24.
    Mitaka T, Tsukada H (1987) Sexual difference in the histochemical characteristics of “altered cell foci” in the liver of aged Fischer 344 rats. Jpn J Cancer Res 78:785–790.PubMedGoogle Scholar

Copyright information

© Springer-Verlag Tokyo 1991

Authors and Affiliations

  • Ryuichi Masuda
  • Michihiro C. Yoshida
    • 1
  • Motomichi Sasaki
    • 2
  • Kimimaro Dempo
    • 1
  • Michio Mori
    • 3
  1. 1.Chromosome Research Unit, Faculty of ScienceHokkaido UniversitySapporo, 060Japan
  2. 2.Sasaki Cancer InstituteChiyoda-ku, Tokyo, 101Japan
  3. 3.Department of PathologySapporo Medical CollegeSapporo, 060Japan

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