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KMID : 0578319970070060777
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Molecules and Cells
1997 Volume.7 No. 6 p.777 ~ p.782
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DNA Cleavage by Hydroxyl Radicals Generated in the Cu,Zn-Superoxide Dismutase and Hydrogen Peroxide System
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Kang Jung-Hoon
Kim Sung-Moon
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Abstract
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To study the catalytic activity of Cu,Zn-superoxide dismutase (SOD) in the generation of hydroxy1 radical (·OH)from H₂O₂we investigated the mechanism of DNA cleavage mediated by human Cu,Zn-SOD and H₂O₂. When plasmid DNA was incubated with 5 ㎛ Cu, Zn-SOD and 1.0 ㎛ H₂O₂DNA cleavage occurred within 15 min. A spectrophotometric study using a 2.2´-azinobis-(3-ethylbenzthiazoline-6-sulfonate) (ABTS) showed that free·OH formation was proportional to concentrations of Cu,Zn-SOD and H₂O₂·OH formation and DNA cleavage were inhibitied by hydroxyl radical scavengers such as cyanide azide, and formate. These results indicated that ·OH generate early in the peroxidative reaction of Cu,Zn-SOD with H₂O₂was implicated in DNA cleavage. Incubation with H₂O₂resulted in a time-dependent release of copper ions from the Cu,Zn-SOD molecule. The released copper ions then likely participated in a Fenton-line reaction to produce ·OH that may have caused DNA cleavage. Evidence that DTPA protected the DNA cleavage induced by the Cu,Zn-SOD/H₂O₂system supports this mechanism. We suggest that DNA cleavage is mediated in the Cu,Zn-SOD/H₂O₂system via the generation of ·OH by a combination of the peroxidative reaction of Cu,Zn-SOD and the Fenton-line reaction of free copper ions feleased from oxidatively damaged SOD.
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