Radiobiological significance of the response of intratumor quiescent cells in vivo to accelerated carbon ion beams compared with gamma-rays and reactor neutron beams

Abstract

Purpose: To clarify the radiobiological significance of the response of intratumor quiescent (Q) cells in vivo to accelerated carbon ion beams and reactor neutron beams.
Materials and Methods: SCC VII tumor-bearing mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all intratumor proliferating (P) cells. Then, they received accelerated carbon ion or gamma-ray irradiation with high dose-rate (HDR) or reduced dose-rate (RDR). Another tumor-bearing mice received reactor thermal or epithermal neutrons with RDR. Immediately after HDR and RDR irradiation or 12 hours after HDR irradiation, the response of Q cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. The frequency in the total (= P+Q) tumor cells was determined from the BrdU non-treated tumors.
Results: The difference in radiosensitivity between total and Q cell populations under gamma-ray irradiation was markedly reduced with reactor neutron beams or accelerated carbon ion beams, especially with a higher linear energy transfer (LET) value. Clearer repair in Q cells than total cells through delayed assay or a decrease in dose-rate under gamma-ray irradiation was efficiently inhibited with carbon ion beams, especially with a higher LET. Under RDR irradiation, accelerated carbon ion beams with a higher LET showed almost similar radiobiological property to reactor thermal and epithermal neutron beams.
Conclusion: In terms of tumor cell-killing effect as a whole, including Q cells, accelerated carbon ion beams, especially with higher LET values, are very useful for suppressing the dependency on the heterogeneity within solid tumors as well as depositing radiation dose precisely.