Abstract
THE ROLE OF OXIDATIVE STRESS AND MITOCHONDRIAL DEFECTS IN GENOMIC INSTABILITY
日本放射線影響学会大会講演要旨集, pp.15-15
日本放射線影響学会大会講演要旨集 日本放射線影響学会第51回大会
2008
DOI: 10.11513/jrrsabst.2008.0.15.0
Abstract
Metabolic oxidative stress and dysfunctional mitochondria have been suggested to play a role in radiation-induced genomic instability but their precise role is unclear. We used hamster fibroblasts (GM10115), genomically unstable (CS-9, LS-12) and stable (114, 118) clones derived from GM10115 following 10 Gy X-ray exposure as a model system. Genomically unstable clones demonstrated increased steady-state levels of reactive oxygen species (ROS) particularly hydrogen peroxide (H2O2) relative to the wild-type and stable clones. In contrast, the genomically stable clones demonstrated increased antioxidant capacity particularly H2O2 scavenging enzymes such as glutathione peroxidase and catalase. Modulating the levels of H2O2 by overexpression of catalase in unstable clones or inhibition of catalase in stable clones, could significantly reduce or increase genomic instability respectively. Furthermore, the unstable clones had depolarized mitochondrial membrane potential and increased mitochondrial content. They also demonstrated increased oxygen consumption, increased mitochondrial electron transport chain complex II activity and improper assembly of complex II suggesting alterations in the electron transfer processes. Intervention in the mitochondrial electron transfer processes using complex II inhibitors was able to reduce H2O2 levels as well as genomic instability in the unstable clones. This work provides clear evidence for mitochondrial oxidative phosphorylation related proteins as targets for radiation injury and augments our understanding of the radiation-induced mutator phenotype. This work suggests that H2O2 scavenging enzymes and complex II inhibitors can reduce radiation-induced genomic instability which is potentially significant for preventing normal tissue injury in patients undergoing radiotherapy.
Details
- Title: Subtitle
- THE ROLE OF OXIDATIVE STRESS AND MITOCHONDRIAL DEFECTS IN GENOMIC INSTABILITY
- Creators
- Disha Dayal - University of IowaSean M Martin - University of IowaKjerstin M Owens - University of IowaAmutha Bominathan - University of Medicine and Dentistry of New JerseyDebkumar Pain - University of Medicine and Dentistry of New JerseyPrabhat C Goswami - University of IowaFrederick E Domann - University of IowaC. Michael Knudson - University of IowaCharles L Limoli - University of CaliforniaDouglas R Spitz - University of Iowa
- Resource Type
- Abstract
- Publication Details
- 日本放射線影響学会大会講演要旨集, pp.15-15
- Conference
- 日本放射線影響学会大会講演要旨集 日本放射線影響学会第51回大会
- Publisher
- 一般社団法人 日本放射線影響学会
- DOI
- 10.11513/jrrsabst.2008.0.15.0
- Language
- Japanese
- Date published
- 2008
- Academic Unit
- Pathology; Fraternal Order of Eagles Diabetes Research Center; Surgery; Radiation Oncology
- Record Identifier
- 9984201256902771
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