Cytotoxic effect of accelerated carbon beams on glioblastoma cell lines with p53 mutation: clonogenic survival and cell-cycle analysis

Abstract

Purpose: The cytotoxic effect of high-LET carbon beams was analysed on p53 mutant and wild-type glioblastoma cell lines.

Materials and methods: Three glioblastoma (U251MG, TK-1, A-172) cell lines, one medulloblastoma (ONS-76) and one fibroblast cell line (NB1RGB) were used. U251MG and TK-1 have mutated p53, A-172, ONS-76 and NB1RGB have wild-type p53. Gamma-ray and 290 MeV/u carbon mono-peak beams with average LET values of 20, 40, 81 and 105keV/microm were used. Cytotoxicity was measured by clonogenic survival assay and DNA histograms were analysed by flow cytometry.

Results: The RBE values for carbon beams at D10 ranged from approximately 1.5-1.7 (20keV) to 2.9-3.1 (105keV). Although p53 mutants were more resistant than wild-types for all radiation qualities, carbon beams yielded a higher RBE in p53 mutants than in wild-types. Alpha values were significantly smaller in p53 mutants than wild-types for gamma- and 20 keV/microm radiations, while no significant difference was noticed for LET greater than 40 keV/microm. A G1 block was noticed after irradiation with gamma-rays and carbon beams of 20 and 40keV/microm in p53 wild-types. A more pronounced G2 block occurred in p53 mutants than wild-types in proportion to LET up to 105 keV/microm.

Conclusion: Accelerated carbon beams can yield higher RBE in gamma-resistant glioblastoma cell lines with p53 mutations. High-LET irradiation induces not only disappearance of the p53-dependent G1 block but also a greater G2 block in glioblastoma cell lines.