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  • Title: K-ras gene mutations in intrahepatic bile duct tumors of Syrian golden hamsters.
    Author: Yamanaka S, Tomioka T, Tajima Y, Okada K, Shiku H, Kanematsu T.
    Journal: J Surg Oncol; 1997 Oct; 66(2):97-103. PubMed ID: 9354164.
    Abstract:
    BACKGROUND AND OBJECTIVES: In our laboratory, we have developed a new model of carcinoma of the bile duct in Syrian golden hamsters, using N-nitrosobis(2-oxopropyl)amine (BOP). Morphologic and biologic characteristics of the carcinoma induced in this model are similar to those seen in humans. In order to examine the gene-related carcinogenesis of intrahepatic bile duct carcinoma, we investigated mutations in the K-ras gene in various early hyperplastic and neoplastic lesions of these hamsters, according to the original sites of the lesions. METHODS: Inbred female hamsters were given a subcutaneous injection of N-nitrosobis(2-oxopropyl)amine (BOP) following dissection of the extrahepatic bile duct on the distal end of the common duct and preparation of a cholecystoduodenostomy (CDDB) or simple laparotomy (SL). Neoplastic lesions arising from the intrahepatic bile duct were histologically examined, and K-ras mutations were investigated. RESULTS: Mutations of K-ras codon 12 were evident in 12% of tubular hyperplasias, 19% of tubular adenocarcinomas, 15% of papillary hyperplasias and 36% of papillary adenocarcinomas. In papillary adenocarcinoma arising from a large bile duct, K-ras mutations occurred more frequently than in tubular adenocarcinoma arising from ductule or ductular proliferation. K-ras mutations were present even in a hyperplasia; the positive rates of the mutations increased in the presence of a carcinoma. Genetic changes in carcinoma of the intrahepatic bile duct varied based on sites of the duct and the histological type. CONCLUSIONS: A part of the hyperplastic lesions of the intrahepatic bile duct presented K-ras gene mutation. This suggests that K-ras gene mutation is an early event in the carcinogenic process. In carcinoma of the intrahepatic bile duct, the lesion arising from a large bile duct of the hepatic hilum tended to exhibit a higher frequency of K-ras gene mutation than did a tubular lesion arising from ductule or ductal proliferation. This hamster model is useful to examine the carcinogenesis of human intrahepatic bile duct carcinoma.
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