1987 Fiscal Year Final Research Report Summary
Studies on the toxicity of deposited tissue iron in iron overload
| Project/Area Number |
60570159
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Okayama University Medical School |
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Principal Investigator |
AWAI Michiyasu 1st. Department of Pathology Okayama University Medical School, 医学部, 教授 (00089898)
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| 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)
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| Project Period (FY) |
1985 – 1987
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| Keywords | Iron overload / Ferric nitrilotriacetate / Active oxygen / Transformation of liver cells / 5)細胞障害 |
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| 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.
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[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
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