Hydrogen peroxide mediates the radiation-induced mutator phenotype in mammalian cells

Author:

Dayal Disha1,Martin Sean M.1,Limoli Charles L.2,Spitz Douglas R.1

Affiliation:

1. Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Centre, The University of Iowa, Iowa City, IA 52242, U.S.A.

2. Department of Radiation Oncology, The University of California, Irvine, CA 92697, U.S.A.

Abstract

Chronic oxidative stress has been associated with genomic instability following exposure to ionizing radiation. However, results showing direct causal linkages between specific ROS (reactive oxygen species) and the ionizing radiation-induced mutator phenotype are lacking. The present study demonstrates that ionizing radiation-induced genomically unstable cells (characterized by chromosomal instability and an increase in mutation and gene amplification frequencies) show a 3-fold increase in steady-state levels of hydrogen peroxide, but not superoxide. Furthermore, stable clones isolated from parallel studies showed significant increases in catalase and GPx (glutathione peroxidase) activity. Treatment of unstable cells with PEG-CAT (polyethylene glycol-conjugated catalase) reduced the mutation frequency and mutation rate in a dose-dependent fashion. In addition, inhibiting catalase activity in the stable clones using AT (3-aminotriazole) increased mutation frequency and rate. These results clearly demonstrate the causal relationship between chronic oxidative stress mediated by hydrogen peroxide and the mutator phenotype that persists for many generations following exposure of mammalian cells to ionizing radiation.

Publisher

Portland Press Ltd.

Subject

Cell Biology,Molecular Biology,Biochemistry

Reference28 articles.

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