| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
Recently we found that KMnOィイD24ィエD2 oxidation of DNA oligomers containing a 7,8-digydro-8-oxoguanine (8-oxo-G) residue induces damage to the neighboring base residues. The present data from several experiments suggested that a redox reaction involving the 8-oxo-G initiates damage: the reactivity of the DNA bases at the site 5'-adjacent to the 8-oxo-G was in the order G > A > T, C, and this preference correlates with the electron donating abilities of the bases. The present study also indicated that other oxidatively damaged bases, 7,8-dihydro-8-oxoadenine (8-oxo-A), 5-hydroxyuracil (5-oh-U) and 5-hydroxycytosine (5-oh-C) show similar behavior in DAN. On the other hand, in order to examine the pathways and the intermediates for the oxidative degradation of 8-oxo-G and 8-oxo-A, we have carried out the KMnOィイD24ィエD2 oxidation using 8-oxo-2'-deoxy-guanosine and -adenosine derivatives as a model. The reactions gave three major products, respectively, and we have determined the structures of the products. Based on the structures, we deduced active oxidation intermediates from the 8-oxo-purines (in DNA) which may be involved in the redox reaction as electron acceptors.
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