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1995 Fiscal Year Final Research Report Summary

Analysis of in vivo hprt mutations in T lymphocytes from atomic bomb survivors.

Research Project

Project/Area Number 05454610
Research Category

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

Allocation TypeSingle-year Grants
Research Field 環境影響評価(含放射線生物学)
Research InstitutionOsaka University

Principal Investigator

KATO Takeshi  Osaka Univ., Faculity of Medicine Assistant Prof., 医学部, 講師 (90028382)

Co-Investigator(Kenkyū-buntansha) FUKUSHIMA Hisao  Osaka Univ., Faculity of Medicine Assistant Prof., 医学部, 助手 (70199214)
Project Period (FY) 1993 – 1995
KeywordsAtomic Bomb Survivors / Somatic Mutations / Peripheral Blood T Cells / HPRT Mutations / Mutation Spectrum
Research Abstract

Akiyama et al., repoted an elevated frequency of 6-thioguanine-resistant (TG^r) mutations at the hypoxanthine-guanine phosphoribosyltransferase (hprt) gene in T cells of peripheral blood from atomic bomb survivors and a slight, but significant, positive correlation between the frequency of mutation and radiation dose. Southern blot analysis of DNA from TG^r mutant T cells of atomic bomb survivors, gowever, failed to show a significant difference between the control and survivor groups. To investigate further the mutational events, we have developed a method by which mutational sequence alterations at the hprt locus can be determined by the combination of, i) the multiplex polymerase chain reaction (PCR) and ii) the RT-PCR of cDNA and sequencing. The numbers of independent TG^r mutant T cell clones examined were 41 from a control group of 18 individuals who had received less than 0.005 Gy, and 50 from an exposed group of 24 individuals who had received more than 1.5 Gy (mean dose, 2.45 <plus-minus> 0.85 Gy) . Gross structural alterations, which were detected by multiplex PCR as a loss of or shift in hprt exon-containing fragments of genomic DNA,were found in 10-15% of the clones from both groups, thus indicating there was no significant difference between them. The altered sequences in the HPRTcDNAs recovered from both groups were of various types. Similar proportions of base substitutions (-45%) , deletions or insertions (-25%) , and exon skipping (-20%) were found in both groups, indicating that neither the gross structural alterations in the genomic DNA nor sequence alterations in the hprt cDNA of both groups differ significantly. These results confirm our previous observation that A-bomb-induced HPRT-mutant T cells mostly have been eliminated from peripheral blood over the decades that have elapsed since exposure.

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Kimura H.: "Molecular nature of x-ray-induced mutations compared with that of spontaneous ones in human c-HPRT gene integrated into mammalian chromosomal DNA." Proceedings of International Conference on Radiation Effects and Protection. Japan Atomic Energy Research Institute,Japan.140-145 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akagi T.: "Specificity of mutations induced by N-methyl-N-nitrosourea in a cDNA of the hprt gene." Carcinogenesis. 14. 725-729 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kimura H.: "Sequence analysis of x-ray-induced mutations occurring in a cDNA of the numan hprt gene integrated into mammalian chromosomal DNA." Radiat Res.134. 202-208 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ogawa, H.: "N-Aceroxy-N-acetyl-2-aminofluorene-induced mutation spectrum in a human hprt c-DNA shuttle vector integrated into mammalian cells." Carcinogenesis. 14. 2245-2250 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kimura H.: "Slippage-misalignment : to what extent dose it contribute to mammalian cell mutagenesis?" Mutagenesis. 6. 395-400 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimahara H.: "Spectrum of in vivo hprt mutations in T lymphocytes from atomic bomb survivors. I. Sequence alterations in cDNA." Carcinogenesis. 16. 583-591 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kagawa Y.: "Analysis of mutations in the human HPRT gene induced by accelerated heavy-ion irradiation." J. Radiat. Res.36. 185-195 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suzuki M.: "LET dependence of cell death,mutation induction and chromatin damage in human cells irradiated with accelerated carbon ions." Adv. Space Res.18. 127-136 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kimura, H.and T.Kato.: "Molecular nature of x-ray-induced mutations compared with that of spontaneous ones in human cHPRT gene integrated into mammalian chromosomal DNA." Proceedings of International Conference on Radiation Effects and Protection. Japan Atomic Energy Research Institute, Japan.140-145 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akagi, T., K.Hiromatsu, H,Ogawa, H.Kimura and T.Kato.: "Specificity of mutations induced by N-methyl-N-nitrosourea in a cDNA of the hprt gene." Carcinogenesis. 14. 725-729 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kimura, H., H.Higuchi, H.Ogawa and T.Kato.: "Sequence analysis of x-ray-induced mutations occurring in a cDNA of the human hprt gene integrated into mammalian chromosomal DNA." Radiat.Res.134. 202-208 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ogawa, H., H.Kimura, M.Kaya, H.Higuchi and T.Kato.: "N-Acetoxy-N-acetyl-2-aminofluorene-induced mutation spectrum in a human hprt c-DNA shuttle vector integrated into mammalian cells." Carcinogenesis. 14. 2245-2250 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kimura, H., H.Ogawa and T.Kato.: "Slippage-misalignment : to what extent dose it contribute to mammalian cell mutagenesis?" Mutagenesis. 9. 395-400 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimahara, H., T.Kato, H.Hirai and M.Akiyama.: "Spectrum of in vivo hprt mutations in T lymphocytes from atomic bomb survivors. I.Sequence alterations in cDNA." Carcinogenesis. 16. 583-591 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] KagawA,Y., F.Yatagai, M.Suzuki, Y.Kase, A.Kobayashi, M.Hirano, T.Kato, M.: "Watanabe, and F.Hanaoka. Analysis of mutations in the human HPRT gene induced by accelerated heavy-ion irradiation." J.Rdiat.Res.36. 185-195 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suzuki, M., M.Watanabe, T.Kanai, Y.Kase, F.Yatagai, T.Kato and S.Matsubara.: "LET dependence of cell death, mutation induction and chromatin damage in human cells irradiated with accelerated carbon ions." Adv.Space Res.vol.18. 127-136 (1996)

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

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Published: 1997-03-04  

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