• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Screening of Biodefense Factors for Toxicity of Environmental Pollutants or Irradiation

Research Project

Project/Area Number 07558201
Research Category

Grant-in-Aid for Scientific Research (A)

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 InstitutionTohoku University

Principal Investigator

NAGANUMA Akira  Tohoku University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (80155952)

Co-Investigator(Kenkyū-buntansha) NISHIYAMA Shoji  Meiji Seika Kaisha Ltd., Pharmaceutical Research Center, Manager, 薬品総合研究所, 主席研究員
MIURA Nobuhiko  Tohoku University, Faculty of Pharmaceutical Sciences, Research Associate, 薬学部, 助手 (20229644)
MIYAIRI Shinichi  Tohoku University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (50209855)
西山 省二  明治製菓(株), 薬品総合研究所, 主席研究員
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1997: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1996: ¥2,400,000 (Direct Cost: ¥2,400,000)
KeywordsEnvironmental Pollutants / Screening / Biodefense Factor / Yeast / Resistance / Methylmercury / Irradiation / 防御遺伝子
Research Abstract

Some biodefense factors, such as antioxidation enzymes or glutathione, against toxicity of environmental pollutants in cells have been known. However, there is the possibility that other factors more important than these known factors are exist in the cells and tissues. Determination of unknown biodefense factors may be essential to evaluate toxicity of the environmental pollutants.
We tried to identify the genes for biodefense factors against toxicity of methylmercury which was selected as a typical environmental pollutant. Yeast clone exhibited resistance to methylmercury was obtained by transfection of plasmid carrying genomic library of yeast. Segregation of the introduced plasmid eliminated methylmercury resistance of the clone, and retransfection of the plasmid isolated from the clone gave methylmercury resistance to the parent yeast. The gene responsible for the methymercury resistance was isolated from the plasmid, and the sequence was examined. Because the protein homologous to the product of this gene has been observed not only in yeast but also in human and other mammals, the gene product may be involved in methylmercury resistance in various species. The gene encodes an enzyme whose activity is inhibited by methylmercury. There is the possibility that the enzyme is a target molecule for methylmercury toxicity.
On the other hand, we also studied the mechanism of protective effect of radiodefense drug, bismuth nitrate, against toxic effect of gamma-irradiation. We found that bismuth compounds induce the synthesis of metallothionein in the bone marrow and metallothionein has a role as biodefense factor for toxic effect of gamma-irradiation. We also found that metallothionein regulates expression of other genes in mammalian cells. There is the possibility that protective effect of metallothionein against gamma-irradiation is due to expression of the gene which encodes a defense factor.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] Satoh, M.: "Enhanced renal toxicity inorganic mercury in metallothionein-null mice" J.Pharmacol.Exp.Ther.283. 1529-1533 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Urano, T.: "Inhibitory effect of selenium on biliary secretion of methyl mercury in rats" Biochem.Biophys.Res.Commun.239. 862-867 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nahanuma, A.: "Overexpression of manhanese-superoxide dismutase prevents methymercury toxicity in HeLa cells" Life Sci.62. PL157-161 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hanada, K.: "Epidermal proliferation of the skin in metallothionein-null mice" J.Invest.Darmatol.(印刷中). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakagawa, I.: "Involvement of oxidative stress in paraquat-induced metallothinein synthesis under glutathione depletion" Free Radic.Biol.Med. (印刷中). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Miyairi, S.: "Determination of metallothionein by high-perfomance liquid chromatography with fluorescence detection using an isocratic solvent system" Anal.Biochem.(印刷中). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakagawa, I., Suzuki, M., Imura, N.and Naganuma, A.: "Enhancement of paraquat toxicity by glutathione depletion in mice in vivo and in vitro." J.Toxicol.Sci.20. 557-564 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakagawa, I., Suzuki, M., Yanagiya, T., Imura, N.and Naganuma, A.: "Effect of glutathione depletion on metallothionein synthesis induced by paraquat in mice." Tohoku J.Exp.Med.177. 249-262 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakagawa, I., Yanagiya, T., Imura, N.and Naganuma, A.: "Induction of renal metallothionein synthesis by cis-diamminedichloroplatinum (II) in glutathione depleted mice." J.Trace Elements Exp.Med.8. 211-219 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakagawa, I., Nishi, E., Naganuma, A.and Imura, N.: "Effect of preinduction of metallothionein synthesis on clastogenicity of anti-cancer drugs in mice." Mutat.Res.348. 37-43 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tohyama, C., Satoh, M., Kodama, N., Nishimura, H., Choo, A., Michalska, A., Kanayama, Y.and Naganuma, A.: "Reduced retention of cadmium in the liver of metallothionein-null mice." Environ.Toxicol.Pharmacol.1. 213-216 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakagawa, I., Satoh, M., Imura, N.and Naganuma, A.: "Role of metallothionein in protection against renal oxidative stress induced by cis-diamminedichloroplatinum (II) in glutathione-depleted mice." Tohoku J.Exp.Med.179. 11-21 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Satoh, M., Nishimura, N., Kanayama, Y., Naganuma, A., Suzuki, T.and Tohyama, C.: "Enhanced renal toxicity by inorganic mercury in metallothionein-null mice." J.Pharmacol.Exp.Ther.283. 1529-1533 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Urano, T., Imura, N.and Naganuma, A.: "Inhibitory effect of selenium on biliary secretion of methyl mercury in rats." Biochem.Biophys.Res.Commun.239. 862-867 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Naganuma, A., Miura, K., Tanaka-Kagawa, T., Kitahara, J., Seko, Y., Toyoda, H.and Imura, N.: "Overexpression of manganese-superoxide dismutase prevents methylmercury toxicity in HeLa cells." Life Sci.62. PL157-161 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hanada, K., Sawada, D., Hashimoto, I., Kida, K.and Naganuma, A.: "Epidermal proliferation of the skin in metallothionein-null mice." J.Invest.Darmatol.(in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Miyairi, S., Shibata, S.and Naganuma, A.: "Determination of metallothionein by high-performance liquid chromatography with fluorescence detection using an isocratic solvent system." Anal.Biochem.(in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tanaka-Kagawa, T., Suzuki, M.Naganuma, A., Yamanaka, N.and Imura, N.: "Strain difference in sensitivity of mice to renal toxicity of inorganic mercury." J.Pharmacol.Exp.Ther.(in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakagawa, I., Suzuki, M., Imura, N.and Naganuma, A.: "Involvement of oxidative stress in paraquat-induced metallothionein synthesis under glutathione depletion." Free Radic.Biol.Med.(in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Satoh, M.: "Enhanced renal toxicity by inorganic mercury in metallothionein-null mice" J.Pharmacol.Exp.Ther.283. 1529-1533 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Urano, T.: "Inhibitory effect of selenium on biliary secretion of methyl mercury in rats" Biochem.Biophys.Res.Commun.239. 862-867 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Naganuma, A.: "Overexpression of manganese-superoxide dismutase prevents methylmercury toxicity in HeLa cells" Life Sci.62. PL157-161 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hanada, K.: "Epidermal proliferation of the skin in metallothionein-null mice" J.Invest.Darmatol.(印刷中). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakagawa, I.: "Involvement of oxidative stress in paraquat-induced metallothionein synthesis under glutathione depletion" Free Radic.Biol.Med. (印刷中). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Miyairi, S.: "Determination of metallothionein by high-performance liquid chromatography with fluorescence detection using an isocratic solvent system" Anal.Biochem.(印刷中). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ippei Nakagawa: "Enhancement of Paraquat Toxicity by Glutathione Ddepletion in Mice in Vivo and in Vitro" J. Toxicol. Sci.20. 557-564 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ippei Nakagawa: "Effect of Preinduction of Metallothionein Synthesis on Clastogenicity of Anticancer Drugs in Mice" Mutation Res.348. 37-43 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ippei Nakagawa: "Induction of Renal Metallothionein Synthesis by cis-Diammine-dichloroplatinum (II) in Glutathione-depleted Mice" J. Trace Elem. Exp. Med.8. 211-219 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ippei Nakagawa: "Effect of Glutathione Depletion on Metallothionein Synthesis Induced by Paraquat in Mice" Tohoku J. Exp. Med.177. 249-262 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Chiharu Thoyama: "Reduced Retention of Cadmium in the Liver of Metallothionein-null Mice" Environ. Toxicol. Pharmacol.1. 213-216 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ippei Nakagawa: "Role of Metallothionein and Glutathione in Protection Against Renal Lipid Peroxidation Induced by cis-dimminedichloroplatinum (II) in Mice" Tohoku J. Exp. Med.179. 11-21 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakagawa, I.: "Effect of preinduction of metallothionein synthesis on clastogenicity of anti-cancer drugs in mice" Mutat. Res.348. 37-43 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nakagawa, I.: "Induction of renal metallothionein synthesis by cis-diammine-dichloroplatinum(II)in glutathione depleted mice" J. Trace Elements Exp. Med.(印刷中). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nakagawa, I.: "Effect of glutathione depletion on metallothionein synthesis induced by paraquat in mice" Tohoku J. Exp. Med.177. 249-262 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nakagawa, I.: "Enhancement of paraquat toxicity by glutathione depletion in mice in vivo and in vitro." J. Toxicol. Sci.20. 557-564 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Thoyama, C.: "Reduced retention of cadmium in the liver of metallothionein-null mice" Environ. Toxicol. Pharmacol.(印刷中). (1996)

    • Related Report
      1995 Annual Research Report

URL: 

Published: 1996-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi