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1991 Fiscal Year Final Research Report Summary

Analysis of mutations induced in cells derived from DNA repair-deficient hereditary disease patients.

Research Project

Project/Area Number 02671046
Research Category

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

Allocation TypeSingle-year Grants
Research Field Human genetics
Research InstitutionKyoto University

Principal Investigator

YAGI Takashi  Kyoto University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (80182301)

Co-Investigator(Kenkyū-buntansha) TAKEBE Hiraku  Kyoto University, Faculty of Medicine, Professor, 医学部, 教授 (10028318)
TATSUMI Junko  Kyoto University, Faculty of Medicine, Instructor, 医学部, 助手 (80128222)
Project Period (FY) 1990 – 1991
KeywordsDNA repair / Mutation / xeroderma pigmentosum / Ataxia telangectasia / Cancer-prone disease / Ultraviolet light / Gamma ray
Research Abstract

To assess the contribution to mutagenesis by DAN repair defects, mutagen-treated shuttle vector plasmids were passed through fibroblasts derived from xeroderma pigmentosum(XP)patients in 3 different DNA repair complementation groups(A, C and F), ataxia telangectasia(AT)patients and mice.
In comparison to DNA repair proficient normal human cells, the UV-treated plasmed passed through the XP-A, C or F cells showed fewer surviving plasmids(XP-A less than C and F)and a higher frequency of mutated plasmids(XP-A greater than C and F). Among base substitution mutations, the major type of the substitution was G : C -> A : T transition in all 3 cell lines. The XP-A, C and F cells revealed a hlgher frequency of G : C -> A : T transition along with a lower frequency of transverslons compared to the normal line. The spectrum of mutations In the XP-A cells was similar to that in the XP-C and F cells. Most single base substitution mutations occurred at G : C base pairs in which the 5'-nelghboring base of the cytosine was a pyrimidine. In spontaneous mutants, more than 50% mutants have a deletion, and the rest have base substitutions with a high frequency of transversions. Among UV-Induced base substitution mutants from mouse cells, 91% mutants have G : C -> A : T transition. gamma -ray-irradiated plasmids passed through AT and normal cells showed no significant difference in the survival and a frequency of mutated plasmed. Efficiency of rejoining of vector DNA restricted by an endonuclease was similar between AT and normal cells, but fidelity of the rejoining is higher in the normal than AT cells. A frequency of methyl nitrosourea-induced mutations, especially G : C -> A : T transition was higher in O^6-alkylguanine-repair deficient mouse cells than the proficient mouse cells.
In this study, a role of DNA repair for the Induction of mutation in molecular level was clarified by using shuttle vectors and DNA repair deficient cells.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Chikako Nishigori: "Altered O^6-alkylguanine-DNA alkyltransferase activity in cell strains originating from mouse skin tumors induced by UV irradiation." Cancer Research. 51. 2425-2429 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takashi Yagi: "Analysis of point mutations in an ultraviolet-irradiated shuttle vector plasmid propagated in cells from Japanese xeroderma pigmentosum patients in complementation groups A and F." Cencer Research. 51. 3177-3182 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mayumi Sato: "Protective effects of sodium selenite on killing and mutation by N-methyl-N^1-nitro-N-nitrosoguanidine in E.coli." Mutation Research. 250. 73-77 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suming Wang: "Reduced DNA repair in progeria cells and effects of γ-ray irradiation on UV-induced unscheduled DNA synthesis in normal and progeria cells." Mutation Research. 256. 59-66 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shin-ichi Moriwaki: "Analysis of N-methyl-N-nitrosourea-induced mutations in a shuttle vector plasmid propagated in mouse O^6-methylguanine-DNA methyltransferase-deficient cells in comparison with proficient cells." Cancer Research. 51. 6219-6223 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takashi Yagi: "UV-induced base substitution mutations in a shuttle vector plasmid propagated in group C xeroderma pigmentosum cells." Mutation Research. (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishigori, C., Moriwaki, S., Yagi, T. and Takebe, H.: "Altered O^6-alkylguanine-DNA alkyltransferase activity in cell strains originating from mouse skin tumors induced by UV irradiation." Cancer Research. 51. 2425-2429 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yagi, T., Tatsumi-Miyajima, J., Sato, M., Kraemer, K. H. and Takebe, H.: "Analysis of point mutations in an Ultraviolet-irradiated shuttle vector plasmid propagated in cells from Japanese xeroderma pigmentosum patients in complementation groups A and F." Cancer Research. 51. 3177-3182 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sato, M., Nunoshiba, T., Nishioka, H., Yagi, T. and Takebe, H.: "Protective effects of sodium selenite on killing and mutation by N-methyl-N' -nitro-N-nitrosoguanidine in E. coli." Mutation Research. 250. 73-77 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wang. S., Nishigori, C., Yagi, T. and Takebe, H.: "Reduced DNA repair in progeria cells and effects of gamma -ray irradiation on UV-induced unscheduled DNA synthesis in normal and progeria cells." Mutation Research. 256. 59-66 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Moriwaki, S., Yagi, T., Nishigori, C., Imamura, S. and Takebe, H.: "Analysis of N-methyl-N-nitrosourea-induced mutations in a shuttle vector plasmid propagated in mouse O^6-methylguanine-DNA methyltransferase-deficient cells in comparison with proficient cells." Cancer Research.51. 6219-6223 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yagi, T., Sato, M., Tatsumi-Miyajima, J. and Takebe, H.: "UV-induced base substitution mutations in a shuttle vector plasmid propagated in group C xeroderma pigmentosum cells." Mutation Research. (1992)

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

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Published: 1993-03-16  

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