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.
Skip Nav Destination
Article navigation
July 2008
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
June 12 2008
Hydrogen peroxide mediates the radiation-induced mutator phenotype in mammalian cells
Disha Dayal;
Disha Dayal
*Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Centre, The University of Iowa, Iowa City, IA 52242, U.S.A.
Search for other works by this author on:
Sean M. Martin;
Sean M. Martin
*Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Centre, The University of Iowa, Iowa City, IA 52242, U.S.A.
Search for other works by this author on:
Charles L. Limoli;
Charles L. Limoli
†Department of Radiation Oncology, The University of California, Irvine, CA 92697, U.S.A.
Search for other works by this author on:
Douglas R. Spitz
Douglas R. Spitz
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.
1To whom correspondence should be addressed (email douglas-spitz@uiowa.edu)
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
December 06 2007
Revision Received:
March 07 2008
Accepted:
March 19 2008
Accepted Manuscript online:
March 19 2008
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem J (2008) 413 (1): 185–191.
Article history
Received:
December 06 2007
Revision Received:
March 07 2008
Accepted:
March 19 2008
Accepted Manuscript online:
March 19 2008
Citation
Disha Dayal, Sean M. Martin, Charles L. Limoli, Douglas R. Spitz; Hydrogen peroxide mediates the radiation-induced mutator phenotype in mammalian cells. Biochem J 1 July 2008; 413 (1): 185–191. doi: https://doi.org/10.1042/BJ20071643
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.