title: Cell cycle checkpoint and apoptosis induction in glioblastoma cells and fibroblasts irradiated with carbon beam.
abstract: This study was conducted in order to evaluate the cytotoxicity of high linear-energy-transfer (LET) ionizing radiation (IR) on glioblastoma cells and fibroblasts using different modes of cell inactivation assays. Two human glioblastoma cell lines with or without p53-mutation, and fibroblasts were used as materials. Gamma rays and 290 MeV/u carbon beams with LET values of 20, 40, 80 keV/mum were used. To evaluate cell inactivation, we used colony formation assay, morphological detection of apoptosis, and flow-cytometry. Serial expressions of p53 and p21 were analyzed by immunoblotting. High-LET IR reduced the reproductive potency of these cells to identical levels in spite of differences in gamma-sensitivity, and yield of cell death correlated to LET values. A p53-wild-type glioblastoma cell line demonstrated a higher yield of apoptosis than other cell lines, whereas fibroblasts hardly displayed any cell death indicating senescence-like growth arrest even after high LET IR. A p53-mutant tumor cell line demonstrated very low yield of cell death with prominent G2/M arrest. Results of radiosensitivity differ according to what mode of cell inactivation is selected. While fibroblasts depend on G1 block after IR, G2/M blocks may play crucial roles in the radioresistance of p53-mutant glioblastoma cells.
authors.affiliation: Proton Medical Research Center, Doctoral Program in Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences, University of Tsukuba. tsuboi-k@md.tsukuba.ac.jp
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuboi
authors.forename: Takashi
authors.initials: T
authors.lastname: Moritake
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Tsuchida
authors.forename: Koichi
authors.initials: K
authors.lastname: Tokuuye
authors.forename: Akira
authors.initials: A
authors.lastname: Matsumura
authors.forename: Koichi
authors.initials: K
authors.lastname: Ando
mesh_terms: D017209:Apoptosis; D002244:Carbon / Q000737:chemistry*; D002453:Cell Cycle / Q000528:radiation effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D016158:Genes, p53; D005909:Glioblastoma / Q000532:radiotherapy*; D006801:Humans; D018499:Linear Energy Transfer; D008856:Microscopy, Fluorescence; D009154:Mutation; D011839:Radiation, Ionizing
chemical_list: D002244:Carbon