Cell cycle checkpoint and apoptosis induction in glioblastoma cells and fibroblasts irradiated with carbon beam

• Published in: Journal of radiation research 2007-07, Vol.48 (4), p.317-325
• Main Authors: Tsuboi, Koji, Moritake, Takashi, Tsuchida, Yukihiro, Tokuuye, Koichi, Matsumura, Akira, Ando, Koichi
• Format: Article
• Language: English
• Subjects: Analysis; Apoptosis; Carbon - chemistry; Cell Cycle - radiation effects; Cell Line, Tumor; Dose-Response Relationship, Drug; Fibroblasts - metabolism; Fibroblasts - radiation effects; Flow Cytometry; Gamma rays; Gene Expression Regulation, Neoplastic - radiation effects; Genes, p53; Glioblastoma - radiotherapy; Glioblastomas; Humans; Linear Energy Transfer; Microscopy, Fluorescence; Mutation; Radiation, Ionizing; Tumor proteins
• ISSN: 0449-3060; 1349-9157; 1349-9157
• DOI: 10.1269/jrr.06081

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.