| Project/Area Number |
04807160
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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 |
Biological pharmacy
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| Research Institution | Kumamoto University School of Medicine |
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Principal Investigator |
MATSUKURA Makoto Kumamoto University School of Medicine Department of Child Development Assistant, 医学部, 助手 (70238997)
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| Co-Investigator(Kenkyū-buntansha) |
KOIKE Kazuhiko University of Tokyo, Faculty of Medicne Department of First Internal Medicine As, 医学部, 助手 (90234658)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1993: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1992: ¥600,000 (Direct Cost: ¥600,000)
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| Keywords | Transgenic mice / HBx gene / Virus induced carcinogenesis / Antisense DNA / Inhibition of carcinogenesis |
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| 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.
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