Research Paper Volume 5, Issue 8 pp 607—622
Therapeutic and space radiation exposure of mouse brain causes impaired DNA repair response and premature senescence by chronic oxidant production
- 1 Department of Biochemistry and Molecular & Cell Biology, Georgetown University Medical Center, Washington, DC 20057, USA
- 2 Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA
- 3 Nuclear Medicine Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892
- 4 Center of Excellence In Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, SA
Received: June 21, 2013 Accepted: August 5, 2013 Published: August 6, 2013
https://doi.org/10.18632/aging.100587How to Cite
Abstract
Despite recent epidemiological evidences linking radiation exposure and a number of human ailments including cancer, mechanistic understanding of how radiation inflicts long-term changes in cerebral cortex, which regulates important neuronal functions, remains obscure. The current study dissects molecular events relevant to pathology in cerebral cortex of 6 to 8 weeks old female C57BL/6J mice two and twelve months after exposure to a γ radiation dose (2 Gy) commonly employed in fractionated radiotherapy. For a comparative study, effects of 1.6 Gy heavy ion56Fe radiation on cerebral cortex were also investigated, which has implications for space exploration. Radiation exposure was associated with increased chronic oxidative stress, oxidative DNA damage, lipid peroxidation, and apoptosis. These results when considered with decreased cortical thickness, activation of cell-cycle arrest pathway, and inhibition of DNA double strand break repair factors led us to conclude to our knowledge for the first time that radiation caused aging-like pathology in cerebral cortical cells and changes after heavy ion radiation were more pronounced than γ radiation.