Altered Oncogene Expression in Hepatocellular Carcinomas Developing Spontaneously in LEC Rats
LEC rats spontaneously suffer hepatitis at around 4 months after birth, enter the chronic phase of hepatitis, and spontaneously develop hepatocellular carcinomas (HCCs) between 1 – 1.5 years after birth . Although dominant oncogene activation in chemically induced HCCs in rats is generally understood to be relatively rare, for the LEC rat, in which an endogenous causative agent appears to be involved, the situation remains unclear. Ha-ras activation has been found with a very high frequency in both chemically induced and spontaneously induced liver carcinomas of B6C3 F1 mice [2–5], but, with the exception of those induced by aflatoxin B1 [6, 7], any type of activated ras was only rarely observed in chemically induced rat liver tumors [4, 8, 9]. We examined HCCs in LEC rats for Ha-, Ki- and N-ras gene mutations. The Polymerase chain reaction (PCR) was adopted for amplifying discrete specific DNA fragments [10, 11], and the sequences were determined directly.
KeywordsHyperplastic Nodule Single Cell Necrosis National Cancer Center Research Institute B6C3FI Mouse Hereditary Hepatitis
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- 8.Watatani M, Perantoni AO, Reed CD, Enomoto T, Wenk ML, Rice JM (1989) Infrequent activation of K-ras, H-ras, and other oncogenes in hepatocellular neoplasms initiated by methyl (acetoxymethyl)-nitrosamine, a methylating agent, and promoted by phenobarbital in F344 rats. Cancer Res 49:1103–1109.PubMedGoogle Scholar
- 18.Nagao M, Sakai R, Kitagawa Y, Ikeda I, Sasaki K, Shima H, Sugimura T (1990) Role of protein phosphatases in malignant transformation. In: Knudson AG, Stanbridge EJ, Sugimura T, Terada M, Watanabe S (eds) Genetic basis for carcinogenesis: Tumor suppressor genes and oncogenes. pp. 177-184, Japan Scientific Society Tokyo/Taylor and Fransis, London.Google Scholar
- 21.Fujimoto Y, Ishizaka Y, Tahira T, Sone H, Takahashi H, Enomoto K, Mori M, Sugimura T, Nagao M (to be published) Possible involvement of c-myc but not ras genes in hepatocellular carcinomas developing after spontaneous hepatitis in LEC rats. Mol Careinogenesis.Google Scholar