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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
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.
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.
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.
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.
Thiollais P, Pourcel C, Dejean A (1985) The hepatitis B virus. Nature 317: 489–495.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Squire RA, Levitt MH (1975) Report of a workshop on classification of specific hepatocellular lesions in rats. Cancer Res 35:3214–3223.
Ward JM (1981) Morphology of foci of altered hepatocytes and naturallyoccurring hepatocellular tumors in F344 rats. Virchows Arch [A] 390:339–345.
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.
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.
Pollard M, Luckert PH (1979) Spontaneous liver tumors in aged germfree Wistar rats. Lab Anim Sci 29:74–77.
Heston WE, Vlahakis G (1968) C3H-Avy — A high hepatoma and high mammary tumor strain of mice. J Natl Cancer Inst 40:1161–1166.
Ward JM, Vlahakis G (1978) Evaluation of hepatocellular neoplasms in mice. J Natl Cancer Inst 61:807–811.
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.
Reuber MD (1969) Influence of hormones on N-2-fluorenyldiacetamide-induced hyperplastic hepatic nodules in rats. J Natl Cancer Inst 43:445–451.
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.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1991 Springer-Verlag Tokyo
About this chapter
Cite this chapter
Masuda, R., Yoshida, M.C., Sasaki, M., Dempo, K., Mori, M. (1991). High Susceptibility to Spontaneous Development of Hepatocellular Carcinoma in LEC Rats. In: Mori, M., Yoshida, M.C., Takeichi, N., Taniguchi, N. (eds) The LEC Rat. Springer, Tokyo. https://doi.org/10.1007/978-4-431-68153-3_6
Download citation
DOI: https://doi.org/10.1007/978-4-431-68153-3_6
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-68155-7
Online ISBN: 978-4-431-68153-3
eBook Packages: Springer Book Archive