The radiosensitivity of total and quiescent cell populations in solid tumors to 290 MeV/u carbon ion beam irradiation in vivo

Abstract

Purpose. To clarify the radiosensitivity of intratumor total and quiescent (Q) cells in vivo to accelerated carbon ion beams compared with γ-ray irradiation. Materials and methods. SCC VII tumor-bearing mice received a continuous administration of 5-bromo-2′-deoxyuridine (BrdU) to label all intratumor proliferating (P) cells. Then they received 290 MeV/u carbon ions or γ-rays. Immediately or 12 hours after the irradiation, the radiosensitivity of Q cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. That of the total (=P+Q) tumor cells was determined from the BrdU non-treated tumors based on the micronucleus frequency and clonogenic cell survival. Results. The apparent difference in radiosensitivity between total and Q cell populations under γ-ray irradiation was markedly reduced with carbon ion beam, especially with a higher linear energy transfer (LET) value. Clearer repair in Q cells than total cells through delayed assay under γ-ray irradiation was efficiently inhibited with carbon ion beams, especially with a higher LET. Conclusion. In terms of tumor cell-killing effect as a whole, including intratumor Q cells, carbon ion beams, especially with higher LET values, were very useful for suppressing the dependency on the heterogeneity within solid tumors as well as depositing radiation dose precisely.