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1993 Fiscal Year Final Research Report Summary

Investigation of inhibition of Hepatitis B virusinduced carcinogenesis in transgenic mice carring HBx gene by use of antisense DNA.

Research Project

Project/Area Number 04807160
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionKumamoto University School of Medicine

Principal Investigator

MATSUKURA Makoto  Kumamoto University School of Medicine Department of Child Development Assistant, 医学部, 助手 (70238997)

Co-Investigator(Kenkyū-buntansha) KOIKE Kazuhiko  University of Tokyo, Faculty of Medicne Department of First Internal Medicine As, 医学部, 助手 (90234658)
Project Period (FY) 1992 – 1993
KeywordsTransgenic mice / HBx gene / Virus induced carcinogenesis / Antisense DNA / Inhibition of carcinogenesis
Research Abstract

First, We investigated how the antisense oligomer (phosphorothioate oligodeoxynucleotides against HBx gene) could be injected into the mice without prominent toxicity. The toxicity appeared to be significant at the dosage, 1mg intraperitoneally (i.p.), in very young mice as young as three weeks old. Therefore, we employed dosage-increment schedule (three days a week) and found that HBx (the promoter gene in Hepatitis B virus : pX gene in Hepatitis B virus) protein n the liver seemed to be reduced in antisense-treated mice compared to control or sense-treated mice.
To confirm the finding above, we treated the 15 weeks old mice every day for one week with 1mg i.p.. The RNA extracted from mice was subjected to RT-PCR and S1 mapping. The level of mRNA in antisensetreated mice appeared to be quite lower than control of sense-treated mice. The mechanism of the activity could be explained as the HBx mRNA is a target of regulation by HBx protein per se.
We will investigate a possibility of anti-tumor activity of the antisense using 1 year old mice, which already developed hepatocellular carcinoma.

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] 松倉誠: "アンチセンスDNAによるAIDS治療の可能性" 医学のあゆみ. 162. 915-917 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 松倉誠: "抗ウイルス剤としてのアンチセンスDNAの展望" 抗ウイルス化学療法研究の進歩. 1. 44-48 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Makoto Matsukura: "Antisense RNA and DNA" Wiley-Liss, 401 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Makoto Matsukura: "Antisense Research and Applications" CRC Press, 579 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Makoto Matsukura: "Possibility of antisense DNA treatment against AIDS" Igakuno-Ayumi. Vol.162 No.13. 915-917 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Makoto Matsukura: "Prospects of Antisense DNA as Anitivirals. Progress of Antiviral Research in Japan" 44-48 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Makoto Matsukura: Regulation of HIV gene expression by antisense oligonucleotides in "Antisense RNA and DNA" (ed.J.A.Murray). Wiley-Liss, N.Y., 285-304 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Makoto Matsukura: Antiviral activities of antisense oligonucleotides against human immunodeficiency virus (HIV), in "Antisense Research and Applications (ed.by S.T.Crooke and B.Lebleu). CRC Press, Boca Raton, 505-520 (1993)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1995-03-27  

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