Background: To investigate the differences between two rat yolk sac tumor cell lines with different radiosensitivities in sensitivity to high-LET heavy ion beam and in sensitizing effect of etoposide (DNA topoisomerase II inhibitor) in combination with heavy ion beam.Material and methods: NMT-1 (wild-type p53 cell) is a parent radiosensitive cell line and NMT-1R (mutant-type p53 cell) is a variant radioresistant cell line. Heavy ion (carbon ion) was accelerated to 290 MeV/u by a heavy-ion medical accerelator in Chiba at National Institute of Radiological Sciences. The dose average LET value in the samples was 80 keV/um. The effects of carbon ion irradiation were assessed by clonogenic assay. The concentration of etoposide required to reduce colony formation by 50% at 1-hour treatment (IC50 of etoposide) was selected for heavy ion irradiation pretreatment for each cell line. The RBE (relative biological effect) of the carbon ion beams to X-rays was calculated for D10 (10% survival dose).Results: There was no significant difference between NMT-1 cells and NMT-1R cells in sensitivity to high-LET heavy ion irradiation (LET;80keV/um) and no shoulder in dose-response curve. The RBE was 1.41 for NMT-1 and 2.16 for NMT-1R, respectively. The RBE of carbon beam was larger in mutant-type p53 cells than in wild-type p53 cells. Etoposide showed a supra-additive effect in combination with carbon beam irradiation in NMT-1R cells. Etoposide potentiation in NMT-1R cells was manifested by the decrease in the slope of the radiation dose-response curve. However, there was no enhancement effect in radiosensitive NMT-1 cells.Conclusions: Our findings suggested that high-LET radiotherapy is expected to be effective for patients carrying radioresistant tumors and mutated p53 tumor cells. Etoposide might be effective for radioresistant tumors in combination with heavy ion beam irradiation.ECCO 1
