Sensitivity of malignant gliom cells against accelerated heavy ion beams

[Purpose]Cytotoxic effect of high LET carbon beams were analyzed on p53 mutant and wide type glioblastoma cell lines using proliferative and interphase cell death as the end-points.Also，the expression of p53 and p21 in glioblastomas cells were analyzed。[Materials and methods]Four glioblastoma(U251 MG，TK-1，A-172，U87 MG)，one medulloblastoma(ONS-76)and one fibroblast cell line(NB1RGB)were used as materials.While U251 MG and TK-1 have mutated p53，other cell lines have wild type p53。Gamma ray and 290 MeV/u carbon mono-peak beams with average LET values from 10to100keV/µm were used。Cytotoxicity was measured by clonogenic survival assay，dye exclusion test，flow-cytometry and apoptosis detection。DNA histograms were analyzed by flow-cytometry.Serial expression of p53 and p27before and after irradiation was analyzed by western blot。[Results]RBE of carbon beams at D-210-D2were ranging from approximately 1.5-1.7(20keV)to2.9-3.1(105keV)。Although p53mutants were more resistant than wild types in all radiation qualities，carbon beams yielded higher RBE in p53mutants than in wild types.More pronounced G2 block occurred in p53mutants than wild types in proportion to LET up to 105keV/µm.Carbon beams yielded significantly higher incidence of cell death as compared to gamma rays.Among thes cell lines，normal skin fibroblast was the most resistant to undergo apoptosis。Up-regulation of p53 and p21 was observed in wild-type U87 MG and NB1 RGB。However，these expressions stayed much longer in NB1 RGB than in U87 MG。[Conclusion]Accelerated carbon beams can yield higher RBE on gamma resistant glioblastoma cell lines with p53mutations.Also，carbon beams can cause cell death more effectively in glioblastoma cells than in fibroblast.

【Purpose】 Cytotoxic effect of high LET carbon beams were analyzed on p53 mutant and wide type glioblastoma cell lines using proliferative and interphase cell death as the end-points. Also, the expression of p53 and p21 in glioblastomas cells were analyzed. 【Materials and methods】 Four glioblastoma (U251MG, TK-1, A-172, U87MG), one medulloblastoma (ONS-76) and one fibroblast cell line (NB1RGB) were used as materials. While U251MG and TK-1 have mutated p53, other cell lines have wild type p53. Gamma ray and 290 MeV/u carbon mono-peak beams with average LET values from 10 to 100 keV/μm were used. Cytotoxicity was measured by clonogenic survival assay, dye exclusion test, flow-cytometry and apoptosis detection. DNA histograms were analyzed by flow-cytometry. Serial expression of p53 and p27before and after irradiation was analyzed by western blot. 【Results】 RBE of carbon beams at DィイD210ィエD2 were ranging from approximately 1.5-1.7 (20 keV) to 2.9-3.1 (105 keV). Although p53 mutants were more resistant than wild types in all radiation qualities, carbon beams yielded higher RBE in p53 mutants than in wild types. More pronounced G2 block occurred in p53 mutants than wild types in proportion to LET up to 105 keV/μm. Carbon beams yielded significantly higher incidence of cell death as compared to gamma rays. Among thes cell lines, normal skin fibroblast was the most resistant to undergo apoptosis. Up-regulation of p53 and p21 was observed in wild-type U87MG and NB1RGB. However, these expressions stayed much longer in NB1RGB than in U87MG. 【Conclusion】 Accelerated carbon beams can yield higher RBE on gamma resistant glioblastoma cell lines with p53 mutations. Also, carbon beams can cause cell death more effectively in glioblastoma cells than in fibroblast.