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Deoxyribonucleoside Triphosphate Imbalance: The Mechanism of Cell Death and DNA-Double Strand Breaks.

Research Project

Project/Area Number 62570989
Research Category

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

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionOkayama University, Faculty of Pharmaceutical Sciences

Principal Investigator

WATAYA Yusuke  Okayama University, Faculty of Pharmaceutical Sciences, 薬学部, 助教授 (90127598)

Co-Investigator(Kenkyū-buntansha) 根岸 和男  岡山大学, 薬学部, 助手 (70116490)
速津 彦哉  岡山大学, 薬学部, 教授 (10012593)
Project Period (FY) 1987 – 1988
Project Status Completed (Fiscal Year 1988)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1988: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1987: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsCell Death / dNTP Imbalance / Nucleotide Metabolism / DNA Strand Breaks / Double Strand Breaks / パルスフィールドゲル電気泳動 / dNTP不均衡死 / デオキシヌクレオシドミリン酸プールの不均衡 / FM3A細胞DNA二本鎖切断 / ヌクレオシド / デオキシヌクレオシドミリン酸 / プールの不均衡 / dNTP Imbalamce Deathi / 制がん剤 / 細胞死の機構 / 5-フルオロウラシル / 代謝拮抗剤
Research Abstract

The mechanism of intracellular deoxyribonucleoside-triphosphate (dNTP)-pool imbalance induced cell death and dNA double strand breaks in mouse FM3A cells was investigated. imbalance of the dNTP pools occurred within 3 h of treatment with 20 m 2-chlorodeoxyadenosine; the dATP and dGTP pools were depleted and the dTTP pool increased. 2-Chlorodeoxyadenosine added to the culture medium broke mature DNA strands, giving fragments of 100-200 kilobase pairs as found by orthogonal-field-alternation gel electrophoresis. DNA strand breaks, measured by this technique, were observed in the treated cells about 12 h after the addition. The cells also lost viability at about 12 h. Breaks in the single and double strands of DNA, as measured by alkaline and neutral filter elution, became evident 18 h after treatment with 20 m 2-chlorodeoxyadenosine; there were as many od single-strand breaks as would be caused by 130 rads of -ray irradiation. Double-strand breaks were equivalent to those caused by 2180 rads of -ray irradiation. Comparison of the ratio of singl- and double-strand breaks caused by 2-chlorodeoxyadenosine to that following radiation suggested that 2-chlorodeoxyadenosine broke only double strands. Cycloheximide inhibited the breakage of DNA double strands and the cell death caused by this compound. Flow cytometric studies of cytostatit brought about by 2-chlorodeoxyadenosine in FM3A cells that cells accumulated in the earlier part of the s phase. 2-Chlorodeoxyadenosine decreased DNA synthesis more than RNA or protein synthesis. The breaks in double strands DNA were probably important in the cell death caused by 2-chlorodeoxyadenosine. The intracellular dNTP imbalance may trigger these events.

Report

(3 results)
  • 1988 Annual Research Report   Final Research Report Summary
  • 1987 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] A.Yoshioka,;S.Tanaka,;O.Hiraoka,;Y.Koyama,;Y.Hirota,;D.Ayusawa,;T.Seno,;C.Garrette,;Y.wataya.: Journal of Biological Chemistry. 262. 8235-8241 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] A.Yoshioka,;S.Tanaka,;O.Hiraoka,;Y.Koyama,;Y.Hirota,;Y.wataya.: Biochemical and Biophysical Research Communications. 146. 258-264 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Y.Hirota,;A.Yoshioka,;S.Tanaka,;K.Watanabe,;T.Otani,;J.Minowada,;A.Matsuda;T.Ueda,;Y.Wataya.: Cancer Research. 49. 915-919 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Y.Wataya,;Y.Hirota,;A.Yoshioka,;S.Tanaka,;T.Otani,;J.Minowada,;A.Matsuda,;T.Ueda.: Nucleic Acids Research,Symposium Series. 20. 51-52 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] A. Yoshioka; S. Tanaka; O. Hiraoka; Y. Koyama; Y. Hirota; D. Ayusawa; T. Seno; C. Garrette; Y. Wataya: "Deoxyribonucleoside-triphosphate imbalance Death : 5-Fluorodeoxyuridine induced DNA double-strand breaks in mouse FM3A cells and the mechanism of cell death." Journal of Biological Chemistry. 262. 8235-8241 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] A. Yoshioka; S. Tanaka; O. Hiraoka; Y. Koyama; Y. Hirota; Y. Wataya: "Deoxyribonucleoside-triphosphate Imbalance Death : Deoxyadenosine induced dNTP imbalance and DNA double-strand breaks in mouse FM3A cells and the mechanism of cell death." Biochemical and Biophysical Research Communications. 146. 258-264 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Y. Hirota; A. Yoshioka; S. Tanaka; K. Watanabe; T. Otani; J. Minowada; A. Matsuda; T. Ueda; Y. Wataya: "Imbalance of deoxyribonucleoside triphosphates, DNA double strand breaks, and cell death caused by 2-chlorodeoxyadenosine in mouse FM3A cells." Cancer Research. 49. 915-919 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Y. Wataya; Y. Hirota; A. Yoshioka; S. Tanaka; T. Otani; J. Minowada; A. Matsuda; T. Ueda: "2-Chlorodeoxyadenosine-induced-dNTP imbalance and DNA double strand breaks in CCRF-HSB2 cells and the mechanism of cell death." Nucleic Acids Research, Symposium Series. 20. 51-52 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] A.Yoshioka,;S.Tanaka,;O.Hiraoka.;Y.Koyama,;Y.Hirota,;D.Ayusawa,;T.Seno,;C.Garrette,;Y.Wataya.: Journal of Biological Chemistry. 262. 8235-8241 (1987)

    • Related Report
      1988 Annual Research Report
  • [Publications] A.Yoshioka,;S.Tanaka,;O.Hiraoka.;Y.Koyama,;Y.Hirota,;Y.Wataya.: Biochemical and Biophysical Research Communications. 146. 258-264 (1987)

    • Related Report
      1988 Annual Research Report
  • [Publications] Y.Hirota,;A.Yoshioka,;S.Tanaka,;K.Watanabe,;T.Otani,;J.Minowada,;A.Matsuda,;T.Ueda,;Y.Wataya.: Cancer Research. 49. 915-919 (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Y.Wataya,;Y.Hirota,;A.Yoshioka,;S.Tanaka,;T.Otani,;J.Minowada,;A.Matsuda,;T.Ueda.: Nucleic Acids Research,Symposium Series. 20. 51-52 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] A. Yoshioka;S. Tanaka;O. Hiraoka;Y. Koyama;Y. Hirota;D. Ayusawa;T. Seno;C. Garrett;Y. Wataya: J. Biol. Chem.262. 8235-8241 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] A. Yoshioka;S. Tanaka;O. Hiraoka;Y. Koyama;Y. Hirota;Y. Wataya: Biochem. Biophys. Res. Commun.146. 258-264 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Y. Wataya;Y. Sonobe;M. Maeda;Z. Yamaizumi;M. Aida;D.V. Santi: J. Chem. Soc. Perkin Trans I. 2141-2147 (1987)

    • Related Report
      1987 Annual Research Report

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Published: 1987-04-01   Modified: 2016-04-21  

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