The Japan Radiation Research Society Annual Meeting Abstracts
The 54th Annual Meeting of The Japan Radiation Research Society
Session ID : PE-4
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Chemical repair of damaged DNA by antioxidant, edaravone
*Kuniki HATAAyumi URUSHIBARAShinichi YAMASHITANaoya SHIKAZONOAkinari YOKOYAYusa MUROYAYosuke KATSUMURA
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Abstract
Radiation damage to DNA originates from DNA radicals directly induced by radiation or through chemical reactions with OH radicals produced in water radiolysis. Generally lifetimes of some DNA radicals are a few seconds (Hildebrand, 1997), which is significantly longer than that of OH radical in biological systems (a few nanoseconds (Roots, 1972)). Thus some reducing agents such as antioxidants may react with DNA radicals to chemically repair them from the radical forms, even under the low concentrations of the chemicals. O'Neill et al. (1983) showed this process by measuring reaction of dGMP radicals with antioxidants. The chemical repair mechanism mediated by antioxidants could be an important radioprotection process in a living system.
Edaravone has clinically been used as an antioxidant for treatment of brain infarct. Recently a radioprotection effect of edaravone in terms of reactive oxidative species (ROS) scavenging was also demonstrated through an in vivo experiment (Anzai, 2004). We infer that such effects can be attributed to its chemical repair property as well as its high reactivity with OH radical. In this study we verify the chemical repair property of edaravone.
At first, edaravone radicals produced in the reaction of edaravone with dGMP radical were observed by pulse radiolysis method. In order to verify the chemical repair of radicals in DNA macromolecules by edaravone we irradiated aqueous solutions of plasmid DNA with gamma-rays. In addition to strand breaks we quantified the chemical yields of AP sites and base lesions using base excision repair enzymes. Productions of AP sites and base lesions were more significantly inhibited than that of strand breaks by addition of edaravone. This result indicates that edaravone can chemically repair DNA radicals resulting in AP sites or base lesions on DNA.
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