Copper, zinc superoxide dismutase enhances DNA damage and mutagenicity induced by cysteine/iron

Citation
Sj. Yoon et al., Copper, zinc superoxide dismutase enhances DNA damage and mutagenicity induced by cysteine/iron, MUT RES-F M, 448(1), 2000, pp. 97-104
Citations number
45
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
ISSN journal
1386-1964 → ACNP
Volume
448
Issue
1
Year of publication
2000
Pages
97 - 104
Database
ISI
SICI code
1386-1964(20000314)448:1<97:CZSDED>2.0.ZU;2-A
Abstract
Oxidative DNA damage caused by a cysteine metal-catalyzed oxidation system (Cys-MCO) comprised of Fe3+, O-2, and a cysteine as an electron donor was e nhanced by copper, zinc superoxide dismutase (CuZnSOD) in a concentration-d ependent manner, as I reflected by the formation of 8-hydroxy-2'-deoxyguano sine (8-OH-dG) and strand breaks. Unlike CuZnSOD, manganese SOD (MnSOD) as well as iron SOD (FeSOD) did not enhance DNA damage. The capacity of CuZnSO D to enhance damage to DNA was inhibited by a spin-trapping agent, 5,5-dime thyl-1-pyrroline N-oxide (DMPO) and a metal chelator, diethylenetriaminepen taacetic acid (DETAPAC). The deoxyribose assay showed that hydroxyl free ra dicals were generated in the reaction of CuZnSOD with Cys-MCO. We found tha t the Cys-MCO system caused the release of free copper from CuZnSOD. CuZnSO D also caused the two-fold enhancement of a mutation in the pUC18 lacZ' gen e in the presence of Cys-MCO when measured as a loss of a-complementation. Based on these results, we interpret the effects of CuZnSOD on Cys-MCO-indu ced DNA damage and mutation as due to reactive oxygen species, probably hyd roxyl free radicals, formed by the reaction of free Cu2+, released from oxi datively damaged CuZnSOD, and H2O2 produced by the Cys-MCO system. (C) 2000 Elsevier Science B.V. All rights reserved.