Iron-mediated induction of sister-chromatid exchanges by hydrogen peroxide and superoxide anion

Abstract

When Chinese hamster fibroblasts were exposed to hydrogen peroxide or to a system consisting of xanthine oxidase and hypoxanthine, which generates superoxide anion plus hydrogen peroxide, sister-chromatid exchanges (SCEs) were formed in a dose-dependent manner. When the iron-complexing agent o-phenanthroline was present in the medium, however, the production of these SCEs was completely inhibited. This fact indicates that the Fenton reaction: Fe 2+ + H 2O 2 → OH 0 + OH − + Fe 3+ is responsible for the production of SCEs. When O 2 − and H 2O 2 were generated inside the cell by incubation with menadione, the production of SCE was prevented by co-incubation with copper diisopropylsalicylate, a superoxide dismutase mimetic agent. The most likely role of O 2 − is as a reducing agent of Fe 3+: O 2 − + Fe 3+ → Fe 2+ + O 2, so that the sume of this and the Fenton reaction, i.e., the iron-catalyzed Haber—Weiss reaction, provides and explanation for the active oxygen species-induced SCE: SCE: H 2O 2 + O 2 − → OH − + OH 0 + O 2. Accorrding to this view, the OH radical thus produced is the agent which ultimately causes SCE. These results are discussed in comparison with other mechanisms previously proposed for induction of SCE by active oxygen species.