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Glutathione/Fe3+/O2-mediated DNA strand breaks and 8-hydroxydeoxyguanosine formation. Enhancement by copper, zinc superoxide dismutase.

作者信息

Park J W, Floyd R A

机构信息

Department of Biochemistry, Kyungpook National University, Taegu, South Korea.

出版信息

Biochim Biophys Acta. 1997 Aug 29;1336(2):263-8. doi: 10.1016/s0304-4165(97)00035-4.

DOI:10.1016/s0304-4165(97)00035-4
PMID:9305798
Abstract

Oxidative DNA damage reflected by the formation of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and strand breaks caused by a glutathione mixed-function oxidation system (GSH-MFO) comprised of Fe3+, O2, and glutathione as an electron donor was enhanced by copper, zinc superoxide dismutase (CuZnSOD) in a concentration-dependent manner. Unlike CuZnSOD, manganese SOD (MnSOD) as well as iron SOD (FeSOD) did not enhance either strand breaks or 8-OH-dH formation in DNA. The capacity of CuZnSOD to enhance damage to DNA was inhibited by 5,5-dimethyl-1-pyrroline N-oxide (DMPO), a spin trapping agent. The salicylate hydroxylation assay showed that hydroxyl radicals formed in the presence of the GSH-MFO system was increased by CuZnSOD. The GSH-MFO system caused the release of free copper from CuZnSOD. Based on these results, we interpret the effects of CuZnSOD on the GSH-MFO induced DNA damage as due to reactive oxygen species, probably .OH, formed by the reaction of free Cu2+, released from oxidatively damaged CuZnSOD, and H2O2 produced by the GSH-MFO system.

摘要

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