| Project/Area Number |
59570129
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Human pathology
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| Research Institution | University of Tokyo |
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Principal Investigator |
SAKAI Masaharu (1986) Faculty of Medicine, University of Tokyo, 医学部, 助手 (50162269)
青木 直人 (1984-1985) 東京大学, 医学部, 助手
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| Co-Investigator(Kenkyū-buntansha) |
AOYAMA Hiromu Faculty of Medicine, University of Tokyo, 医学部, 助手 (50167805)
AOKI Naoto Faculty of Medicine, University of Tokyo, 医学部, 助手 (20159289)
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| Project Period (FY) |
1984 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1986: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1985: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1984: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Hepatitis B virus (HBV) / DNA / HBV DNA integration / Hepatocellular carcinoma / Liver cirrhosis / Multicentric origin of hepatocellular carcinoma / 肝細胞増生 / クローン |
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| Research Abstract |
In this project, we analyzed hepatitis B virus (HBV) DNA replication patterns and integration patterns into the host genome among different part of the liver tissues and hepatocellular carcinoma (HCC) tissues. In one investigation, we analyzed HBV DNA integration patterns of three hepatocellular carcinoma nodules (HCCN) in the liver of a HBV infected patient by Southern blot hybridization. We found HBV DNA integration pattern of one HCCN was completely different from those of other two. We think this indicates different clonal origin, i.e. multicentric origin, of HCC in this case. We believe this is the first confirmation of multicentric origin of HCC at molecular level. In the next investigation, we analyzed the difference of HBV DNA replication patterns and integration patterns among the nodules of the liver cirrhosis (LC). In this investigation, we found the HBV DNA replication patterns are heterogeneous among the nodules of LC. We also found HBV DNA integration patterns among the nodules of LC are heterogeneous and no common integration patterns are found among the nodules of LC and HCC. These results indicate: 1) HBV DNA integrates into the host genome and integration sites relative to the restriction enzyme cutting sites are different from one liver cirrhosis nodules (LCN) to another and probably different from one cell to another. 2) In some LCN, some of these cells with integrated HBV DNA grow clonally. 3) Replication of HBV DNA is not homogeneous among LCN and one small specimen such as biopsy materials cannot represent every areas of the cirrhotic liver. This phenomenon should be kept in mind in the interpretation of the biopsy material as an indicator of virus replication state of a patient.
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