Low-dose/dose-rate γ radiation depresses neural differentiation and alters protein expression profiles in neuroblastoma SH-SY5Y cells and C17.2 neural stem cells.
The effects of low doses of ionizing radiation on cellular development in the nervous system are presently unclear. The focus of the present study was to examine low-dose γ-radiation-induced effects on the differentiation of neuronal cells and on the development of neural stem cells to glial cells. Human neuroblastoma SH-SY5Y cells were exposed to (137)Cs γ rays at different stages of retinoic acid-induced neuronal differentiation, and neurite formation was determined 6 days after exposure. When SH-SY5Y cells were exposed to low-dose-rate γ rays at the onset of differentiation, the number of neurites formed per cell was significantly less after exposure to either 10, 30 or 100 mGy compared to control cells. Exposure to 10 and 30 mGy attenuated differentiation of immature C17.2 mouse-derived neural stem cells to glial cells, as verified by the diminished expression of glial fibrillary acidic protein. Proteomic analysis of the neuroblastoma cells by 2D-PAGE after 30 mGy irradiation showed that proteins involved in neuronal development were downregulated. Proteins involved in cell cycle and proliferation were altered in both cell lines after exposure to 30 mGy; however, the rate of cell proliferation was not affected in the low-dose range. The radiation-induced attenuation of differentiation and the persistent changes in protein expression is indicative of an epigenetic rather than a cytotoxic mechanism.
Centre for Radiation Protection Research, Department of Genetics, Microbiology and Toxicology, The Arrhenius Laboratories for Natural Science, Stockholm University, Sweden.
Ainars
A
Bajinskis
Heléne
H
Lindegren
Lotta
L
Johansson
Mats
M
Harms-Ringdahl
Anna
A
Forsby
D000818:Animals; D002454:Cell Differentiation / Q000528:radiation effects*; D045744:Cell Line, Tumor; D005720:Gamma Rays; D005904:Glial Fibrillary Acidic Protein; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000032:analysis; D009419:Nerve Tissue Proteins / Q000032:analysis; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D016501:Neurites / Q000528:radiation effects; D009447:Neuroblastoma / Q000473:pathology*; D020543:Proteome; D014212:Tretinoin / Q000494:pharmacology
D005904:Glial Fibrillary Acidic Protein; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D020543:Proteome; C528900:glial fibrillary astrocytic protein, mouse; D014212:Tretinoin