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Mechanisum of radiation induction of genomic instability

Research Project

Project/Area Number 09680523
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 環境影響評価(含放射線生物学)
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

NIWA Ohtsura  Kyoto University, Radiation Biology Center, Professor, 放射線生物研究センター, 教授 (80093293)

Co-Investigator(Kenkyū-buntansha) YOSHIKAWA Isao  Nagasaki University, Faculty of Environmental Sciences, 環境科学部, 教授 (80039528)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1998: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsIonizing radiation / Genomic instability / Mouse minitatellite / Paternal irradiation / Material mutation / Early stage embryos / 放射線 / 遺伝的不安定性 / ミニサテライト / マウス / ショウジョウバエ / 眼色遺伝子 / 精子DNA損傷 / 受精卵・初期胚 / 体細胞突然変異 / w^<iv>遺伝子
Research Abstract

Induction of genomic instability was investigated by analyzing length change mutation of mouse minisatellite locus, Pc-1, in F1 mice born to irradiated male mice. Mutant frequency of the paternally derived as well as the maternally derived allele of the locus among F1 born to unirradiated males were around 10%. The paternally derived allele of the locus exhibited a higher frequency of mutation when the male parents were irradiated at the spermatogonia, spermatid and spermatozoa stages. The mutant frequency was highest when the mice were irradiated at the spermatid stage. The mutant frequency at the dose of 1 Gy to spermatid stage was around 22%. Therefore, the excess mutant frequency is over 10% which is too high to be due to the direct consequence of radiation induced DNA in the genome. This suggests that the length change mutation is the secondary effect of genomic instability induced by radiation. In order to prove the indirect nature of the mutation induction, male mice were irradi … More ated at the spermatozoa stage and F1 mice were studied for the mutation at the maternally derived locus. Investigation of more than 100 F1 mice revealed that the mutant frequency of the maternally derived allele in F1 born to 6 Gy irradiated males was elevated to 20%, which is similar to that of the paternally derived allele. This value was statistically significant. This indicates that the DNA damage introduced into oocyte by irradiated sperm inflict genomic instability, which act in cis on the paternal genome as well as in trans on the maternal genome to mutate the Pc-1 locus. In addition to mouse minisatellite, the reversion of the white-ivory mutation at the maternally derived white locus of Drosophilla melanogaster was studied in F1 flies born to spermatozoa irradiated male with the white mutation. In this system, the reversion frequency at the maternally derived allele was also elevated by irradiation of spermatozoa. Thus, the present investigations demonstrate that radiation mutates minisatellite sequences indirectly through induced genomic instability in oocytes and in cells of early stage embryos. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] O.Niwa、他: "A defect in cell to cell adhesion via integrin-fibronectin interactins observed in a highly metastatic tumor cell line."Biochem.Biophys.Res.Commun.. 230. 407-412 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] O.Niwa、他: "A defect in cell to cell adhesion via integrin-fibronectin interactins observed in a highly metastatic tumor cell line."Jpn.J.Cancer Res.. 88. 67-71 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] O.Niwa、他: "Allelic loss analysis of g-ray-induced thmic lymphomas:Two candidate tumor suppressor gene loci on chromosome 12 and 16."Leukemia. 11. 285-286 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] O.Niwa、他: "Allelic loss analysis of g-ray-induced thmic lymphomas:Two candidate tumor suppressor gene loci on chromosome 12 and 16."Ongogene.. 16. 2747-2754 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] O.Niwa、他: "p53 gene mutation and loss of heterozygosity of chromosome 11 in methylcholanthrene induced mouse sarcomas."Jpn.J.Cancer Res.. 89. 269-277 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] I.Yoshikawa、他: "The relative biological effectiveness of accelerated carbon ions with different LET for inducing mitotic crossing over and intragenic reversion of the white-ivory allele in Drosophila larvae."Int.J.Radiat.Biol.. 74. 239-248 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] O. Niwa et al.: "Allelic loss analysis of g-ray-induced thmic lymphomas : two candidate tumor suppressor gene loci on chromosome 12 and 16"Ongogene. 16. 2747-2754 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] O. Niwa et al.: "p53 gene mutation and loss of heterozygosity of chromosome 11 in methylcholanthrene-induced mouse sarcomas"Jpn. J. Cancer Res.. 89. 269-277 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] O. Niwa et al.: "Emerging frontier in low dose radiobiology""Trends in Radiation and Carcinogenesis", Forshungszentrum Julich GmbH, Julich. 1-11 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] I. Yoshikawa et al.: "The relative biological effectiveness of accelerated carbon ions with different LET for inducing mitotic crossing over and intragenic reversion of the white-ivory allele in Drosophila larvae"Int. J. Radiat. Biol.. 74. 239-48 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] O.Niwa他: "Allelic loss analysis of g-ray-induced thmic lymphomas : two candidate tumor suppressor gene loci on chromosome 12 and 16." Ongogene. 16. 2747-2754 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] O.Niwa他: "p53 gene mutation and loss of heterozygosity of chromosome 11 in methylcholanthrene-induced mouse sarcomas." Jpn.J.Cancer Res.89. 269-277 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] I.Yoshikawa他: "The relative biological effectiveness of accelerated carbon ions with different LET for inducing mitotic crossing over and intragenic reversion of the white-ivory allele in Drosophila larvae." Int.J.Radiat.Biol.74. 239-248 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] O.Niwa他: "Analysis of the c-myc,K-ras and p53 genes in methylcholanthrene-induced mouse sarcomas." Jpn.J.Cancer Res.90. 40-47 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] O.Niwa他: "Accumulation of recombinant chromosomes and low fidelity of transmission of chromosome X DNA markers in gamma-ray-induced lymphomas lacking p53." Mol Carcinog.24. 57-63 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] O.Niwa他: "Mutations in the p53 and Scid genes do not cooperate in lymphomagenesis in doubly heterozygote mice." Biochem.Biophys.Res.Commun.255. 99-103 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] O.Niwa他: "“Trends in Radiation and Carcinogenesis",Forshungszentrum Julich GmbH,Julich." Emerging frontier in low dose radiobiology., 1-11 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] N.Koide、他: "Accumulation of recombinant chromosomes and low fidelity in chromosome transmission detected in γ-ray induc lymphomas lacking p53 using inactive X chromosome as a probe" Cancer Res.印刷中. (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Matsumoto, 他: "Allelic loss analysis of γ-ray-induced thmic lymphomas:two candidate tumor suppressor gene loci on chromosome 12 and 16." Ongogene. 印刷中. (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Shimokado, 他: "p53 gene mutation and loss of hererozygosity of chromosome ll in methylcholanthrene-induced mouse sarcomas." Jpn.J.Cancer Res.印刷中. (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] S.Tashiro、他: "Nuclear proteins binding to the recombination hotspot region of the retinoic acid receptor alpha gene." Leukemia. 11,. 285-286 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Abe、他: "A defect in cell to cell adhesion via integrin-fibronectin interactins observed in a highly metastatic tumor cell line" Jpn.J.Cancer Res.88. 64-71 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] N.Kotomura、他.: "Transcriptional regulatin by competition between ELP isoforms and nuclear receptors." Biochem.Biophys.Res.Commun.230. 407-412 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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