Study on pathogenesis of hepatocholangioma I n mice

Research Project

Project/Area Number	08660389
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Applied veterinary science
Research Institution	Nippon Veterinary and Animal Science University
Principal Investigator	KIMIMASA Takahashi Nippon Veterinary and, Animal Science University, Associate Professor, 獣医畜産学部, 助教授 (40277661)
Co-Investigator(Kenkyū-buntansha)	HARADA Takahiko Nippon Veterinary and, Animal Science University, Professor, 獣医畜産学部, 教授 (70060530)
Project Period (FY)	1996 – 1997
Project Status	Completed (Fiscal Year 1997)
Budget Amount *help	¥400,000 (Direct Cost: ¥400,000) Fiscal Year 1997: ¥400,000 (Direct Cost: ¥400,000)
Keywords	hepatocholangioma / oval cell / choline-deficient diet / 2-acetyl aminofluorene / mice / 肝細胞癌 / 2-acetylaminofluorene / vinyl carbamate / oval細胞 / 2-Acetylaminofluorene
Research Abstract	Oval cell have been shown to have a capacity differentiate into hepatocyte or biliary ductullar cell. This study was conducted to determine whether oval cells are associated with histogenesis of hepatocholangiocarcinoma (HCC), a malignant tumor in mice that consists of two types of cells with ductullar or hepatocellular phenotype B6C3F1 male and female mice were fed choline deficient diet and administered 2-acetyl aminofluorene (AAF) by gavage (0. 1mg/corn oil/g body weight) 4 times a week. A cycle of treatment consist of 3 or 4 weeks on choline deficiency-AAF followed by 1 week on normal diet, and was repeated for 15 months. The regimen causes oval cell proliferation and relatively rapid induction of liver cancer in rats. B6C3F1 male and female pups were given a single 0.1 ml intraperitoneal injection of 0.15 μM/g body weight and observed for 12 months. Livers from the animals subjected to interim and terminal kill were examined histopathologically. Tumor masses were seen in males and females of VC-treated group after 9 months of treatment, while in AAF-treated group the first onset was 12 months in males and no tumor occurred in females during the study. In VC-treated animals, there was a progressive development from hepatocellular foci to adenomas, and ultimately to carcinomas. On the other hand, slight proliferation of oval cells was persistently seen in periportal area of AAF-treated animals just till the first onset of tumor. The morphology of tumor seen in AAF-treated animals was similar to that in VC-treated ones. No hepatocholangiocarcinoma was observed in any animals. It is concluded that oval cells are not related to hepatocarcinogenesis induced by VC treatment. Oval Cell proliferation induced by choline deficiency-AAF regimen here seemed not to be associtated with tumor development, because the number of oval cells was smaller compared to the data reported in other rodent study