The LEC Rat pp 320-325 | Cite as

Replicative and Unscheduled DNA Synthesis of LEC Rat Hepatocytes: Relevance to Natural Development of Hepatocellular Carcinoma

  • Norimasa Sawada
  • Hirohumi Sakamoto
  • Hidetoshi Takahashi
  • Katsuhiko Enomoto
  • Yumiko Oyamada
  • Michio Mori


The LEC rat is a new mutant inbred strain which suddenly displays coagulative necrosis of hepatocytes at around 4 months after birth [1], for which a single autosomal recessive gene (hts gene, [2]) is responsible. Those LEC rats surviving with chronic hepatitis eventually develop hepatocellular carcinomas as they become old [1, 3–5]. Since this hepatitishepatocellular carcinoma sequence is quite similar to the development of human liver cancer, LEC rats are expected to serve as an excellent animal model for the study of human hepatocarcinogenesis.


Chronic Hepatitis Partial Hepatectomy Human Liver Cancer Excellent Animal Model Human Hepatocarcinogenesis 
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  1. 1.
    Yoshida MC, Masuda R, Sasaki M, Takechi N, Kobayashi H, Dempo K, Mori M (1987) New mutation causing hereditary hepatitis in the laboratory rat. J Hered 78:361–365.PubMedGoogle Scholar
  2. 2.
    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
  3. 3.
    Masuda R, Yoshida MC, Dempo K, Mori M (1988) High susceptibility to hepatocallular carcinoma development in LEC rats with hereditary hepatitis. Jpn J Cancer Res 79:825–835.Google Scholar
  4. 4.
    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 glutathion S-transferese-positive foci in the livers of LEC rats. Jpn J Cancer Res 79:5–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Sawaki M, Enomoto K, Takahashi H, Nakajima Y, Mori M (1990) Phenotype of preneoplastic and neoplastic liver lesions during spontaneous liver carcinogenesis of LEC rats. Carcinogenesis 11:1875–1861.CrossRefGoogle Scholar
  6. 6.
    Takahashi H, Enomoto K, Nakajima Y, Mori M (1990) High sensitivity of the LEC rat liver to the carcinogenic effect of diethylnitrosamine. Cancer Lett 51:247–250.PubMedCrossRefGoogle Scholar
  7. 7.
    Sugiyama T, Takeichi N, Kobayashi H, Yoshida MC, Sasaki M, Taniguchi N (1988) Metabolic predisposition of a novel mutant (LEC rats) to hereditary hepatitis and hepatomas; Alterations of the drug metabolizing enzymes. Carcinogenesis 9:1569–1572.PubMedCrossRefGoogle Scholar
  8. 8.
    Grisham JW, Kaufmann, WK, Kaufman DG (1983) The cell cycle and chemical carcinogenesis. Surv Synth Pathol Res 1:49–66.Google Scholar
  9. 9.
    Farber E (1980) The sequential analysis of liver cancer induction. Biochim Biophys Acta 605:149–166.PubMedGoogle Scholar
  10. 10.
    Pitot HC Sirica AE (1980) The stages of initiation and promotion in hepatocarcinogenesis. Biochim Biophys Acta 605:191–215.PubMedGoogle Scholar
  11. 11.
    Craddock VM Frei JV (1974) Induction of liver cell adenomata in the rat by single treatment with N-methyl-N-nitresourea given at various times after partial hepatectomy. Br J Cancer 30:503–511.PubMedCrossRefGoogle Scholar
  12. 12.
    Ishikawa T, Takayama S, Kitagawa T (1980) Correlation between time of partial hepatectomy after a single treatment with diethylnitrosamine and induction of adenosinetriphosphatase-deficient islands in rat liver. Cancer Res 40:4261–4264.PubMedGoogle Scholar
  13. 13.
    Setlow RB (1978) Repair deficient disorders and cancer. Nature 271:713–717.PubMedCrossRefGoogle Scholar
  14. 14.
    Grisham JW (1980) Cell types in long-term propagable cultures of rat liver. Ann NY Acad Sci 394:128–137.CrossRefGoogle Scholar
  15. 15.
    Marceau, N. (1990) Cell lineages and differentiation programs in epidermal, urothelial and hepatic tissues and their neoplasmas. Lab Invest 63:4–20.PubMedGoogle Scholar
  16. 16.
    Ogawa K, Mukai H, Mori M (1985) Effect of aging on proliferative activity of normal and carcinogen-altered hepatocytes in rat liver after a two-thirds partial hepatectomy. Jpn J Cancer Res 76:779–784.PubMedGoogle Scholar
  17. 17.
    Sawada N, Ishikawa T (1988) Reduction of potential for replicative but not unscheduled DNA synthesis in hepatoytes isolated from aged as compared to aging rats. Cancer Res 48:1617–1622.Google Scholar

Copyright information

© Springer-Verlag Tokyo 1991

Authors and Affiliations

  • Norimasa Sawada
  • Hirohumi Sakamoto
  • Hidetoshi Takahashi
  • Katsuhiko Enomoto
  • Yumiko Oyamada
  • Michio Mori
    • 1
  1. 1.Department of PathologySapporo Medical CollegeSapporo, 060Japan

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