2004 Fiscal Year Final Research Report Summary
Oxidative damage to DNA and nucleotide and its prevention
| Project/Area Number |
12213137
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | University of Occupational and Environmental Health |
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Principal Investigator |
KASAI Hiroshi Institute of Industrial Ecological Sciences, professor, 産業生態科学研究所, 教授 (40152615)
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| Co-Investigator(Kenkyū-buntansha) |
KAWAI Kazuaki Institute of Industrial Ecological Sciences, assistant professor, 産業生態科学研究所, 助教授 (60161262)
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| Project Period (FY) |
2000 – 2004
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| Keywords | 8-OH-dG / OGG1 / MTH1 / Orf135 / 2-OH-ATP / 8-Cl-dGTP |
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| Research Abstract |
Following results were obtained during 5 years. 1) Ribonucleotide 2-OH-ATP was efficiently hydrolyzed by human MTH1 protein ; 2) After administration of azo dye, 3'-methyl-4-dimethylaminoazobenzen to mice and rats, 8-OH-dG in DNA and its repair activity in liver were increased. These results suggested that oxidative stress is involved in the liver carcinogenesis ; 3) 8-Chloro-dGTP, a hypochlorous acid-modified nucleotide, is hydrolyzed by hMTH1, the human MutT homolog ; 4) 8-hydroxyguanine leves in DNA, its repair activity, and hOGG1 and hMTH1 mRNA expression in human lung alveolar epithelial cells were induced by crocidolite asbestos treatment ; 5) The oxidized pyrimidine ribonucleotide, 5-hydroxy-CTP, was hydrolyzed efficiently by the Escherichia coli recombinant Orf135 protein ; 6) Acute arsenite treatment induced 8-hydroxyguanine formation in DNA and inhibition of repair activity in cultured human cells ; 7) A new automated method to analyze urinary 8-hydroxydeoxyguanosine by a high-performance liquid chromatography-electrochemical detector system was developed ; 8) In the liver of 3'-methyl-4-dimethylamino-azobenzene-treated mouse, a smaller, 32-kDa 8-oxoguanine DNA glycosylase was detected ; 9) During caspase-dependent apoptosis, a mouse OGG1 fragment was detected. A relationship between Oxidative DNA damage and apoptosis was suggested.
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