Journal article
Hydrogen peroxide mediates the radiation-induced mutator phenotype in mammalian cells
Biochemical journal, Vol.413(1), pp.185-191
07/01/2008
DOI: 10.1042/BJ20071643
PMCID: PMC2677991
PMID: 18352860
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-amino-triazole) 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.
Details
- Title: Subtitle
- Hydrogen peroxide mediates the radiation-induced mutator phenotype in mammalian cells
- Creators
- Disha Dayal - University of IowaSean M. Martin - University of IowaCharles L. Limoli - University of California, IrvineDouglas R. Spitz - Holden
- Resource Type
- Journal article
- Publication Details
- Biochemical journal, Vol.413(1), pp.185-191
- Publisher
- Portland Press Ltd
- DOI
- 10.1042/BJ20071643
- PMID
- 18352860
- PMCID
- PMC2677991
- ISSN
- 0264-6021
- eISSN
- 1470-8728
- Number of pages
- 7
- Grant note
- R01CA100045; P30CA086862 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 07/01/2008
- Academic Unit
- Pathology; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984312976202771
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