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Human risk assessment of environmental toxicants based on apoptotic signaling system.

Research Project

Project/Area Number 10558091
Research Category

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

Allocation TypeSingle-year Grants
Section展開研究
Research Field 環境影響評価(含放射線生物学)
Research InstitutionNational Institute for Environmental Studies

Principal Investigator

ISHIDO Masami  National Institute for Environmental Studies, Regional Environment Division, Senior Researcher, 地域環境研究グループ, 主任研究員 (60211728)

Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsenvironmental toxicants / apoptosis / human risk assessment / cadmium / apoptosis-related oncogenes / 血中アポトーシス シグナル
Research Abstract

The objective of this study is to develop a new means for human risk assessment of environmental toxicants based on apoptotic signaling systems. To achieve the aims, it is necessary to detect the apoptotic signals in human serum, which were triggered by the environmental toxicants such as the heavy metals and diesel exhaust particles. It was hard to detect DNA fragmentation in serum as an apoptotic signal by the conventional methods. It therefore had to be overcome the issue of the low amount of the fragment in the serum.
PCR methods made it possible : more than 50 ng DNA fragment was detectable by ligating the 12-mer adaptor to the fragment, followed by PCR amplification. However. this method is still to be improved because of artifacts in the serum.
It is important to reveal the molecular mechanism of environmental toxicants-mediated apoptotic pathways in order to apply it for human risk assessment of therm earlier and with higher sensitivity. There were several molecules that were induced by exposure of cells to cadmium : Bc1-2 was identified as a new defense player and both c-myc and metallothionein were not involved in cadmium-induced apoptotic events. The death molecule' for cadmium cytotoxicity remains to be un clear.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] M.Ishido, et al.: "Transcriptional regulation of c-jun during inhibition by selenite of methylmercury-induced apoptosis of rat C6 glioma cells"Res.Adv.In Neurochem.. 1. 13-22 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Ishido, et al.: "Regulation of cell fate by cadmium and zinc."J.Health Sci. 47(1). 9-13 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujimaki et al.: "Induction of apoptosis in mouse thymocytes by cadmium."Toxicol.Lett.. 115. 99-105 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Ishido, et al.: "Zinc stimulates DNA synthesis during its anti-apoptotic action, independently with increments of an anti-apoptotic proteins, Bcl-2 in porcine kidney LLC-Pk_1 cells."J.Pharmacol.Exp.Ther.. 290. 923-928 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Ishido, et al.: "Cadmium-bound metallothionein induces apoptosis in rat kidneys, but not in cultured kidney LLC PK_1 cells."Life Sciences. 64(9). 797-804 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Ishido, et al.: "C-MYC is not involved in cadmium-elicited apoptotic pathway in porcine kidney LLC-PK_1 cells."Life Sciences. 63(14). 1195-1204 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Ishido and M.Kunimoto.: "Regulation of cell fate by cadmium and zinc."J.Health Sci.. 47. 1-5 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Ishido and M.Kunimoto.: "Transcriptional regulation of c-Jun during inhibtion by selenite of methylmercuryinduced apoptosis of rat C6 glioma cells."Res. Adv. Neurochem.. 1. 13-22 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujimaki, M.Ishido, and K.Nohara.: "Induction of apoptosis in thymocytes by cadmium."Toxicol. Lett.. 115. 99-105 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Ishido, T.Suzuki, T.Adachi. and M.Kunimoto.: "Zinc stimulates DNA synthesis during its antiapoptotic action independently with increments of an antiapoptotic protein, Bc1-2, in porcine kidney LLC-PK_1 cells"J.Pharmacol. Exp.. Ther, 290. 923-928 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Ishido and T.Suzuki.: "Cadmium-bound metallothionein induces apoptosis in rat kidneys, but not in cultured kidney LLC-PK_1 cells."Life Sci.. 64. 797-804 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Ishido and T.Suzuki.: "c-Myc is not involved in cadmium-elicited apoptotic pathway in porcine kidney LLC-PK cells."Life Sci.. 63. 1195-1204 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Ishido, et al.: "Transcriptional regulation of c-jun during inhibition by selenite of methylmercury-induced apoptosis of rat C6 glioma cells"Res.Adv.In Neurochem.. 1. 13-22 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Ishido, et al.: "Regulation of cell fate by cadmium and zinc."J.Health Sci. 47(1). 9-13 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujimaki et al.: "Induction of apoptosis in mouse thymocytes by cadmium."Toxicol.Lett.. 115. 99-105 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Ishido, et al.: "Regulation of cell fate by metals"J.Health Sci. (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fujimaki et al.: "Induction of apoptosis in mouse thymocytes by cadmium"Toxicol.Lett.. (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Ishido et al.: "Zinc stimulates DNA synthesis during its anti-apoptotic action, independently with increments of an anti-apoptotic proteins, Bcl-2 in porcine kidney LLC-Pk_1 cells"J.Pharmacol.Exp.Ther.. 290. 923-928 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Ishido, et al.: "Cadmium-bound metallothionein induces apoptosis in rat kidneys, but not in cultured kidney LLC PK_1 cells"Life Sciences. 64(9). 797-804 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Ishido, et al.: "C-MYC is not involved in cadmium-elicited apoptotic pathway in porcine kidney LLC-PK,cell." Life Sciences. 63(14). 1195-1204 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Ishido, et al.: "Cadmium-bound metallothionein induces apoptosis in rat kidneys, but not in cultured kidney LLC-PK_1 cells." Life Sciences. 64(9). 797-804 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Ishido, et al.: "Zinc stimulates DNA synthesis during its anti-apoptotic action, independently with increments of an anti-apoptotic proteins, Bcl-2 in porcine kidney LLC-Pk_1 cells." J.Pharmacol.Exp.Ther.(発表予定). (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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