| Project/Area Number |
12670463
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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 | The University of Tokyo |
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Principal Investigator |
MORITA Kyoji The Univ. of Tokyo, Dpt. of. Medicine, assistant professor, 医学部・附属病院, 講師 (00272550)
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| Co-Investigator(Kenkyū-buntansha) |
KOIKE Kazuhiko The Univ. of Tokyo, Dpt. of. Medicine, assistant professor, 医学部・附属病院, 助教授 (80240703)
FUJIE Hajime The Univ. of Tokyo, Dpt. of. Medicine, assistant professor, 医学部・附属病院, 助手 (90332577)
SHINTANI Yoshizumi The Univ. of Tokyo, Dpt. of. Medicine, assistant professor, 医学部・附属病院, 助手
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | Hepatitis C virus / transgenic mouse / ROS / hydroperoxide / alcohol / 脂質 |
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| Research Abstract |
We developed transgenic mice coexpressing hepatitis C virus (HCV) core protein and hepatitis B virus (HBV) x protein to investigate a role of HBV in hepatocarcinogenesis in patients with chronic hepatitis C and occult HBV infection.
we explored the oxidant/antioxidant status in the liver of a HCV core gene transgenic mouse model of HCC in HCV infection, prior to development of HCC, by sequential quantification of hydroperoxide level, glutathione level and catalase activity and comparison of these parameters with those of age-matched non-transgenic control mice. We found an age-dependent increase in oxidative stress in the livers of transgenic mice which develop HCC in the absence of inflammation as a consequence of core protein expression. Our results indicate that the HCV core protein induces reactive oxygen species (ROS) in the liver in the absence of inflammation, which may, in part, be responsible for the development of HCC in this mouse model as well as in chronic hepatitis C patients. We also showed alcohol caused a market increase in hydroperoxide level in transgenic mice, suggesting synergism between alcohol and HCV in hepatocarcinogenesis.
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