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

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.