| Project/Area Number |
14570531
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Tokyo Metropolitan Organization for Medical Research |
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Principal Investigator |
WAKITA Takaji Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Department of Microbiology, Research Scientist, 東京都神経科学総合研究所, 副参事研究員 (40280789)
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| Co-Investigator(Kenkyū-buntansha) |
YASUI Kotaro Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Department of Microbiology and Immunology, Research Scientist, 東京都神経科学総合研究所, 参事研究員 (90073080)
MIYAMOTO Michiko Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Department of Microbiology and Immunology, Research Scientist, 東京都神経科学総合研究所, 研究員 (40190821)
KATO Takanobu Nagoya City University, Graduate School of Medical Sciences, Department of Clinical Molecular Informative Medicine, Assistant Professor, 大学院・医学研究科・共同研究教育センター, 助手 (20333370)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | HCV / TRANSGENIC MOUSE / CCL4 / Heoatocarcinogenesis / トランスジェニックマウス / 四塩化炭素 / 慢性肝障害 / 肝発癌 |
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| Research Abstract |
Although hepatitis C virus (HCV) is a well known causative agent of hepatocellular carcinoma (HCC), the mechanism by which HCV induces HCC remains obscure. To elucidate the role of HCV in hepatocarcinogenesis, a model of hepatocyte injury was established using HCV core transgenic mice, which were developed using C57BL/6 mice transfected with the HCV core gene under control of the serum amyloid P component promoter. After 18 -24 months, neither steatosis nor hepatic tumors were found in transgenic mice. The extent of hepatocyte injury and tumorigenesis were then examined in transgenic mice following repeated administration of carbon tetrachloride (CCl4) using various protocols (20%: 1/week,10%: 2/week and 20%: 2/week). Serum alanine aminotransferase (ALT) levels did not differ among HCV core transgenic mice and non-transgeriic littermates, however, after 40 weeks, hepatic adenomas preferentially developed in transgenic mice receiving 20% CCl4 once weekly. Moreover, HCC was observed in transgenic mice receiving 2 weekly injections of a 20% solution of CCl4,and not observed in the non-transgenic control mice. In conclusion, the HCV core protein did not promote hepatic steatosis or tumor development in the absence of hepatotoxicity. However, the HCV core protein promoted adenoma and HCC development in transgenic mice following repeated CCl4 administration. These results suggest that hepatotoxicity resulting in an increased rate of hepatocyte regeneration enhances hepatocarcinogenesis in HCV infected livers. Furthermore, this experimental mouse model provides a valuable method by which to investigate hepatocarcinogenesis.
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