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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
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1991: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1990: ¥1,300,000 (Direct Cost: ¥1,300,000)
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.

Report

(3 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 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
    • Related Report
      1991 Final Research Report Summary
  • [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
    • Related Report
      1991 Final Research Report Summary
  • [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
    • Related Report
      1991 Final Research Report Summary
  • [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
    • Related Report
      1991 Final Research Report Summary
  • [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
    • Related Report
      1991 Final Research Report Summary
  • [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
    • Related Report
      1991 Final Research Report Summary
  • [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
    • Related Report
      1991 Final Research Report Summary
  • [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
    • Related Report
      1991 Final Research Report Summary
  • [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
    • Related Report
      1991 Final Research Report Summary
  • [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
    • Related Report
      1991 Final Research Report Summary
  • [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
    • Related Report
      1991 Final Research Report Summary
  • [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
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Chikako Nishigori: "Altered O^6ーalkylguanineーDNA alkyltransferase activity in cell Strains originating from mouse skin tumors induced by UV irradiation." Cancer Research. 51. 2425-2429 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Takashi Yagi: "Analysis of point mutations in an ultravioletーirradiated shuttle vector plasmid propagated in cells from Japanese xeroderma pigmentosum patients in complementation groups A and F." Cancer Research. 51. 3177-3182 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Mayumi Sato: "Protective effects of sodium selenite on killing and mutation by NーmethylーN'ーnitroーNーnitrosoguanidine in E.coli." Mutation Research. 250. 73-77 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Suming Wang: "Reduced DNA repair in progeria cells and effects of γーray irradiation on UVーinduced unscheduled DNA synthesis in normal and progeria cells." Mutation Research. 256. 59-66 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Shinーichi Moriwaki: "Analysis of NーmetylーNーnitrosoureaーinduced mutations in a shuttle vector plasmid propagated in mouse O^6ーmethylguanineーDNA methyltransferaseーdeficient cells in comparison with proficient cells." Cancer Research. 51. 6219-6223 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Takashi Yagi: "UVーinduced base substitution mutations in a shuttle vector plasmid propagated in group C xeroderma pigmentosum cells." Mutation Research. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Takashi Yagi: "Analysis of Point Mutations in a UVーirradiated Shuttle Vector Plasmid Propagated in Cells from Japanese Xeroderma Pigmentosum Patients in Complementation Groups A and F." Cancer Research. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Chikako Nishigori: "Altered O^6ーalkylguanineーDNA alkyltransferase activity in cell strains originating from mouse skin tumors induced by UV irradiation." Cancer Research. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] 佐藤 まゆみ: "金属の突然変異抑制作用とその機構ーセレンを中心にー" 環境変異原研究. (1991)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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