1997 Fiscal Year Final Research Report Summary
Screening of Biodefense Factors for Toxicity of Environmental Pollutants or Irradiation
| Project/Area Number |
07558201
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
環境影響評価(含放射線生物学)
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| Research Institution | Tohoku University |
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Principal Investigator |
NAGANUMA Akira Tohoku University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (80155952)
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| 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)
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| Project Period (FY) |
1995 – 1997
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| Keywords | Environmental Pollutants / Screening / Biodefense Factor / Yeast / Resistance / Methylmercury / Irradiation |
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| 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.
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[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)
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[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)
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[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)
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