ABSTRACT
Ionizing radiation is known to cause cell apoptosis at high dose range, but little is known about the cellular response to low dose radiation. In this study, we found that conditioned medium harvested from WI-38 lung fibroblasts and H1299 lung adenocarcinoma cells exposed to 0.1Gy to 1Gy could enhance the migration and invasion of unirradiated H1299 cells in both 2D and 3D culturing circumstances. Low dose radiation did not induce apoptosis, but induced senescence in irradiated cells. We next examined the expression of immediately early genes including c-Myc and K-Ras. Although both genes could be up-regulated by low dose radiation, induction of c-Myc was more specific to low dose range (0.5Gy) at transcriptional and translational levels. Knockdown of c-Myc by shRNA could repress the senescence induced by low dose radiation. The conditioned medium of irradiated cells induced migration of unirradiated cells was also repressed by knockdown of c-Myc. The c-Myc inhibitor 10058-F4 could suppress low dose radiation induced cell senescence, and the conditioned medium harvested from irradiated cells pretreated with 10058-F4 also lost the ability to enhance the migration of unirradiated cells. The cytokine array analysis revealed that immunosuppressive monocyte chemoattractant protein-1 increased by low dose radiation could be repressed by 10058-F4. We also showed that 10058-F4 could suppress low dose radiation induced tumor progression in a xenograft tumor model. Taken together, current data suggest that -Myc is involved in low dose radiation induced cell senescence and potent bystander effect to increase the motility of unirradiated cells.
Subject(s)
Cellular Senescence/radiation effects , DNA-Binding Proteins/genetics , Dose-Response Relationship, Radiation , Fibroblasts/metabolism , Fibroblasts/radiation effects , Transcription Factors/genetics , Adenocarcinoma of Lung/metabolism , Cell Line , Fibroblasts/pathology , Humans , Lung , Lung Neoplasms/metabolism , Proto-Oncogene Proteins p21(ras)/genetics , Transcription, Genetic/radiation effectsABSTRACT
We have used aqueous NaMnO4 solution as the deintercalation and oxidation agent to treat gamma-Na0.7CoO2 powders and to successfully obtain superconducting sodium cobalt oxyhydrates, Nax(H2O)yCoO2, with onset Tc approximately 4.6 K without using highly toxic Br2/CH3CN solution. Chemical analyses indicate that the sodium content x decreases with increasing concentration of NaMnO4 solution and depends slightly on the immersion time. Unlike using a high concentration of aqueous KMnO4 as the deintercalation and oxidation agent, all the hydrated products are the c approximately 19.6 A phase with bilayers of water molecules intercalated between the CoO2 layers and sodium layers because of the absence of K+ in the Na+ layers.
