Irradiation With Carbon Ion Beams Induces Apoptosis, Autophagy, and Cellular Senescence in a Human Glioma-Derived Cell Line
- Department of Virology and Preventive Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma (Japan)
- 21st Century Center of Excellence Program for Biomedical Research Using Accelerator Technology, Maebashi, Gunma (Japan)
- Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma (Japan)
- Microbeam Radiation Biology Group, Radiation-Applied Biology Division, Quantum Beam Science Directorate, Japan Atomic Energy Agency, Takasaki, Gunma (Japan)
Purpose: We examined biological responses of human glioma cells to irradiation with carbon ion beams (C-ions). Methods and Materials: A human glioma-derived cell line, NP-2, was irradiated with C-ions. Apoptotic cell nuclei were stained with Hoechst 33342. Induction of autophagy was examined either by staining cells with monodansylcadaverine (MDC) or by Western blotting to detect conversion of microtuble-associated protein light chain 3 (MAP-LC3) (LC3-I) to the membrane-bound form (LC3-II). Cellular senescence markers including induction of senescence-associated beta-galactosidase (SA-beta-gal) were examined. The mean telomere length of irradiated cells was determined by Southern blot hybridization. Expression of tumor suppressor p53 and cyclin/cyclin-dependent kinase inhibitor p21{sup WAF1/CIP1} in the irradiated cells was analyzed by Western blotting. Results: When NP-2 cells were irradiated with C-ions at 6 Gy, the major population of the cells died of apoptosis and autophagy. The residual fraction of attached cells (<1% of initially irradiated cells) could not form a colony: however, they showed a morphological phenotype consistent with cellular senescence, that is, enlarged and flattened appearance. The senescent nature of these attached cells was further indicated by staining for SA-beta-gal. The mean telomere length was not changed after irradiation with C-ions. Phosphorylation of p53 at serine 15 as well as the expression of p21{sup WAF1/CIP1} was induced in NP-2 cells after irradiation. Furthermore, we found that irradiation with C-ions induced cellular senescence in a human glioma cell line lacking functional p53. Conclusions: Irradiation with C-ions induced apoptosis, autophagy, and cellular senescence in human glioma cells.
- OSTI ID:
- 21367610
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 76, Issue 1; Other Information: DOI: 10.1016/j.ijrobp.2009.08.054; PII: S0360-3016(09)03021-1; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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