Therapeutic and space radiation exposure of mouse brain causes impaired DNA repair response and premature senescence by chronic oxidant production.
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 ion 56Fe 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.
Department of Biochemistry and Molecular and Cell Biology, Georgetown University Medical Center, Washington, DC 20057, USA.
Shubhankar
S
Suman
Olga C
OC
Rodriguez
Thomas A
TA
Winters
Albert J
AJ
Fornace
Chris
C
Albanese
Kamal
K
Datta
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D059447:Cell Cycle Checkpoints / Q000528:radiation effects; D016922:Cellular Senescence / Q000528:radiation effects*; D002540:Cerebral Cortex / Q000473:pathology / Q000502:physiology / Q000528:radiation effects*; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays; D005904:Glial Fibrillary Acidic Protein; D015227:Lipid Peroxidation / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin / Q000378:metabolism; D018384:Oxidative Stress / Q000528:radiation effects; D011839:Radiation, Ionizing; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation / Q000528:radiation effects
D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D064231:Nestin; D017382:Reactive Oxygen Species; C528900:glial fibrillary astrocytic protein, mouse