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Studies on the toxicity of deposited tissue iron in iron overload

Research Project

Project/Area Number 60570159
Research Category

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

Allocation TypeSingle-year Grants
Research Field Experimental pathology
Research InstitutionOkayama University Medical School

Principal Investigator

AWAI Michiyasu  1st. Department of Pathology Okayama University Medical School, 医学部, 教授 (00089898)

Co-Investigator(Kenkyū-buntansha) KAWABATA Teruyuki  1st. Department of Pathology Okayama University Medical School, 医学部, 助手 (60201448)
SADAHIRA Yoshito  1st. Department of Pathology Okayama University Medical School, 医学部, 助手 (90144740)
HAYASHI Keiki  1st. Department of Pathology Okayama University Medical School, 医学部, 助教授 (70033222)
定平 吉都  岡山大学, 医学部, 助手 (30178694)
Project Period (FY) 1985 – 1987
Project Status Completed (Fiscal Year 1987)
Budget Amount *help
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1987: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1986: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1985: ¥800,000 (Direct Cost: ¥800,000)
KeywordsIron overload / Ferric nitrilotriacetate / Active oxygen / Transformation of liver cells / 5)細胞障害 / 鉄過剰症 / ヘモジデリン / 酸素ラジカル / 鉄錯体 / 鉄の細胞障害
Research Abstract

Ferric nitrilotriacetate (Fe^<3+>-NTA) is a weak iron chelate compound. Repeated intraperitoneal injection of this solution to rats and rabbits induced an iron overload similar to human hemochromatosis.
This solution showed maximum absorbance at pH7.5. The iron was in a ferric high spin state and coordinated octahedrally with a relatively symmetric structure and also probably heptagonally. A spin trapping technique employing 5,5-dimethyl-l-pyrroline-N-oxide (DMPO) yields a DMPO spin adduct of unknown redical with three doublets (DMPO-Z) in the Fe^<3+>-NTAsolution. The DMPO-Z signal was suppressed by a decrease in oxygen tension, -tochopherol and 3-tert-butyl-4-hydroxy anisol (BHA). The Fe^<3+>-NTA solution produced a strong DMPO-OH signal in the presence of H_2O_2.
The cytotoxic effect of Fe^<3+>-NTA on normal rat liver epithelial cells (RL-34) cultured in medium contaning 10% fetal calf serum was studied. Marked cytolysis was present in cells exposed to 50<micrn>g/ml iron. The remaining cells showed anomalus growth, namely cell pileup and aggregation. They can be grown on soft agar culture system. A subcutaneous innoculation of these cells (5x10^6) to new born rats made a tumor in each of all five rats within three weeks.
Lung metastasis was found in three out of these five rats. The results showed that active oxygen generated with Fe^<3+>-NTA in the medium was responsible for the transformation of the liver cells in culture.

Report

(2 results)
  • 1987 Final Research Report Summary
  • 1986 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Kawabata,T.;Awai,M.;Kohono,M.: Acta Med. Okayama. 40. 163-173 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Nakamoto,S.;Yamanoi,Y.;Kawabata,T.;Sadahira,Y;Mori,M.;Awai,M.: Biochimica et Biophysica Acta. 889. 15-22 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Awai,M.: Acta Haematologica Japonica. 49. 1650-1659 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 山田雅保,沖垣達,粟井通泰: 組織培養. 13. 47-52 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 粟井通泰,川端晃幸: 組織培養. 13. 53-58 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Yamada,M.;Okigaki,T.;Awai,M.: Cell Structure and Function. 12. 407-420 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Ozaki,M.;Kawabata,T.;Awai,M.: Bioclem.J.250. 598-595 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Ogino, T.;Awai, M.: Biochimica et Biophysica Acta. 958. 388-395 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Kawabata, T., Awai, M., Kohono, M.: "Generation of active oxygen species by Iron Nitrilotriacetate (Fe-NTA)" Acta Med. Okayama. 40. 163-173 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Nakamoto, S., Yamanoi, Y., Kawabata, T., Sadahira, Y., Mori, M., Awai, M.: "Lipid peroxidation and cytotoxicity of Ehrlich ascites tumor cells by ferric nitrilotriacetate." Biochimica et Biophysica Acta. 889. 15-22 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Awai, M.: "Experimental iron overload using ferric nitrilotriacetate (Fe^<3+>-NTA): A proposal model of the diseases in man caused by iron overload." Acta Haematologica Japonica.49. 1650-1659 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Yamada, M., Okigaki, T., Awai, M.: "Role of superoxide radicals in cytotoxic effects of Fe-NTA on cultured normal liver epithelial cells." Cell Structure and Function. 12. 407-420 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Ozaki, M., Kawabata, T., Awai, M.: "Iron release from haemosiderin and production of iron catalysed hydroxyl radical in vitro." Biochem. J.250. 589-595 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Ogino, T., Awai, M.: "Lipid peroxidation and tissue injury by ferric citrate in paraquat-intoxecation mice." Biochimica et Biophysica Acta. 958. 388-395 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Teruyuki Kawabata: Acta Med.Okayama. 40(3). 163-173 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Shu Nakamoto: Biochimica Biophysica. 889. 15-22 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Michiyasu Awai: Acta Haematologica Japonica. 49(8). 154-155 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Michiyasu Awai: Acta Haematologica Japonica. 49(8). 186-195 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 山田雅保: 組織培養. 13(2). 47-52 (1987)

    • Related Report
      1986 Annual Research Report
  • [Publications] 粟井通泰: 組織培養. 13(2). 53-58 (1987)

    • Related Report
      1986 Annual Research Report

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Published: 1987-03-31   Modified: 2016-04-21  

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