@article{oai:repo.qst.go.jp:00045758, author = {Jinno-Oue, Atsushi and Shimizu, Nobuaki and Hamada, Nobuyuki and Wada, Seiichi and Tanaka, Atsushi and Shinagawa, Masahiko and Ohtsuki, Takahiro and Mori, Takahisa and N., Saha Manujendra and S., Hoque Ariful and Islam, Salequl and Kogure, Kimitaka and Funayama, Tomoo and Kobayashi, Yasuhiko and Hoshino, Hiroo and 浜田 信行}, issue = {1}, journal = {International Journal of Radiation Oncology Biology Physics}, month = {Dec}, note = {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(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(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.}, pages = {229--241}, title = {Irradiation with carbon ion beams induces apoptosis, autophagy, and cellular senescence in a human glioma-derived cell line}, volume = {76}, year = {2009} }