| Research Abstract |
An experimental model for the induction of extrahepatic biliary duct carcinomas in hamsters given cholecystoduodenostomy with dissection of the extrahepatic duct at the distal end of the common duct (CDDB) followed by N-nitrosobis(2-oxopropyl)amine (BOP) has been reported. The CDDB procedure greatly accelerates cell turnover in the biliary epithelium. In the present experiment, mutations of K-ras and p53 genes in the induced lesions were investigated by the RT-PCR-SSCP method followed by direct sequencing. Mutations of K-ras, involving a G to A transition in second position of codon 12 of K-ras exon 1, were detected in 6 out of 8 (75%) extrahepatic bile duct carcinomas and 6 out of 11 (54.5%) pancreatic duct carcinomas. However, no mutations of p53 were observed in either tumor type. The results indicate an association between anomalous pancreaticobiliary junction and development of biliary carcinomas that may be pertinent to the human situation, and indicate that condition of the mode
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l predispose to mutations occurring in K-ras but not p53.
Then we followed the hamsters given CDDB procedure without BOP, and evaluated the biliary carcinogenesis of this model. A total of 20 female 7 weeks old Syrian golden hamsters were given CDDB procedure. All hamsters were fed a basal diet and provided drinking water ad libitum without any carcinogen until sacrifice. 6 hamsters were sacrificed 6 month after CDDB, and hyperplasia of the gallbladder epithelium was observed in all of them. PCNA labeling indices of the gallbladder were 8.4±2.2% in normal hamsters, but were 56.2±11.4% in hamsters given CDDB procedure. 14 hamsters were sacrificed 1 year after the surgery, and hyperplasia of the gallbladder epithelium was also observed in all of them. Extrahepatic bile duct carcinoma was observed in one out of 14 -hamsters. Histologically, moderately differentiated adenocarcinoma cells were observed proliferating in the lumen of bile ducts and invading to extra-bile duct tissue. The CDDB procedure greatly accelerates cell turnover in the extrahepatic biliary system. We can observe the extrahepatic biliary carcinogenesis in this model without Less
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