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Infulence of p53 on the induction of mouse skin tumors by repetitive beta-irradiation

Research Project

Project/Area Number 16310046
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Risk sciences of radiation/Chemicals
Research InstitutionUniversity of Occupational and Environmental Health, Japan

Principal Investigator

OOTSUYAMA Akira  University of Occupational and Environmental Health, Japan, School of Med., Assoc. Prof. (10194218)

Co-Investigator(Kenkyū-buntansha) NORIMURA Toshiyuki  University of Occupational&Environmental Health, Japan, School of Med., Prof. (20039530)
KATO Fumio  University of Occupational&Environmental Health, Japan, School of Med., Res. Assoc. (20309959)
Project Period (FY) 2004 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥7,010,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2004: ¥2,800,000 (Direct Cost: ¥2,800,000)
KeywordsP53 gene / KO mouse / Beta-irradiation / repetitive irradiation / skin cancer / radiation carcinogenesis
Research Abstract

Introduction: We studied about a protection mechanism of p53 gene against a radiation induced teratogenesis using p53 (-/-) mice (KO), a p53 (+/-) mice (hetero) and a p53 (+/+) mice (wild). In wild mice, p53 dependent and independent DNA repair mechanisms restore DNA damages together, and then unrestorable damage cells are removed by p53 dependent apoptosis effectively after low dose rate radiation (LDR). Therefore the teratogenic rate keeps control level. On the other hand, in a KO mice, p53 independent DNA repair mechanism works, but p53 dependent DNA repair mechanism and apoptosis don' t work. So the teratogenic rate does not decrease to a control level at even low dose rate irradiation in KO mice. (Kato F, et. al. Int. J. Radiat. Biol. 77, 13-, 2001) In the DNA damage after LDR, it is thought there are similar mechanisms in processes of carcinogenesis and teratogenesis. In this study, with the mice same as an above it, we investigate whether a p53 gene has mechanisms to remove dama … More ges by not only DNA repair mechanism but also apoptosis on radiation carcinogenesis process. In wild mice, if a repair of DNA damages and removing of damage cells by apoptosis are almost completely performed on repetitive LDR, the cancer might not occur. But under the same experimental condition, if the cancer occurs in KO mice, it is thought there is a threshold dose on radiation carcinogenesis process.
Method: Seven weeks old mice were used. The backs of the mice were irradiated with beta-rays three times a week until occurrence of tumor or throughout the life of the mice. Beta-rays source: <90>Sr^-^<90>Y disk, 1.85GBq, 15Gy/min. Group I: 2.SGy/day. Group II: 5Gy/day. P53 genes extracted from the tumors were analyzed about LOH and mutation.
Results: In KO mice, we did not found occurrence of tumor. In hetero mice, we found 8/21 and 25/45 of tumor incidence in Group I and Group II. In wild mice, we found 2/8 and 6/33 of tumor incidence in Group I and Group II, and appearance time of the tumors was about 150days later than that of hetero mice. In hetero mice, 17/26 of tumors had LOH of p53 but had not mutations. In wild mice, 7/9 of tumors had mutations and 1/7 of tumor had LOH.
Conclusion: An existence state of a p53 gene affects the tumor-causing time and incidence obviously. Types of variation of a p53 gene may be different by an existence state of a p53 gene Less

Report

(5 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (10 results)

All 2007

All Journal Article (3 results) Presentation (7 results)

  • [Journal Article] Influence of p53 on the induction of mouse skin tumors by repetitive beta-irradiation.2007

    • Author(s)
      Aklra OOTSUYAMA
    • Journal Title

      1 3th International Congress of Radiation Research, San Francisco, USA.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Induction of mouse skin tumors by repetitive beta-irradiation : influence of a p53 gene.2007

    • Author(s)
      Akira OOTSUYAMA
    • Journal Title

      The 51th Annual Meeting of the Japan Radiation Research SocIety, Makuhari, Chiba.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Induction of skin cancer by repeated beta-irradiation : A role of p53 gene.2007

    • Author(s)
      Akira OOTSUYAMA
    • Journal Title

      The 144th Annual Meting of Japanese Society of Veterinaly Science, Ebetsu, kkaido.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] β線による皮膚発がんの発生率と発生時期はp53遺伝子の存在状態に依存2007

    • Author(s)
      大津山 彰
    • Organizer
      第50回日本放射線影響学会
    • Place of Presentation
      千葉県幕張市
    • Year and Date
      2007-11-15
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] lnduction of mouse skin tumors by repetitive beta-lrradiation : lnffuence of a p53 gene.2007

    • Author(s)
      Akira OOTSUYAMA
    • Organizer
      The 51st Annual Meeting of the Japan Radlation Research Sodety
    • Place of Presentation
      Makuhari, Chiba
    • Year and Date
      2007-11-15
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 放射線による発がんの発生率と発生時期はp53遺伝子の存在状態に依存する2007

    • Author(s)
      大津山 彰
    • Organizer
      第144回日本獣医学会
    • Place of Presentation
      北海道江別市
    • Year and Date
      2007-09-02
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] lnduction of skin cancer by repeated beta-irradiation : A role of p53 gene2007

    • Author(s)
      Akira OOTSUYAMA
    • Organizer
      The 144th Annual Metlng of Japanese Society of Veterlnaly Science
    • Place of Presentation
      Ebetsu, Hokkaido
    • Year and Date
      2007-09-02
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Influence of p53 on the induction of mouse skin tumors by repetitive beta-irradiation2007

    • Author(s)
      Akira OOTSUYAMA
    • Organizer
      13th.International Congress of Radiation Research
    • Place of Presentation
      San Francisco,USA
    • Year and Date
      2007-07-10
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] lnfluence of p530 on the induction of mouse skin tumors by repetitive beta-lrradlatlon.2007

    • Author(s)
      Akira OOTSUYAMA
    • Organizer
      13th lnternational Congress of Radiation Research
    • Place of Presentation
      San Frandsco USA
    • Year and Date
      2007-07-10
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Influence of p53 on the induction of mouse skin tumors by repetitive beta-irradiation2007

    • Author(s)
      Akira OOTSUYAMA
    • Organizer
      13th International Congress of Radiation Research
    • Place of Presentation
      San Francisco,USA
    • Year and Date
      2007-07-10
    • Related Report
      2007 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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