Radiobiologic Significance of Response of Intratumor Quiescent Cells In Vivo to Accelerated Carbon Ion Beams Compared With γ-Rays and Reactor Neutron Beams

Purpose To clarify the radiosensitivity of intratumor quiescent cells in vivo to accelerated carbon ion beams and reactor neutron beams. Methods and Materials Squamous cell carcinoma VII tumor-bearing mice were continuously given 5-bromo-2′-deoxyuridine to label all intratumor proliferating cells. Next, they received accelerated carbon ion or γ-ray high-dose-rate (HDR) or reduced-dose-rate (RDR) irradiation. Other tumor-bearing mice received reactor thermal or epithermal neutrons with RDR irradiation. Immediately after HDR and RDR irradiation or 12 h after HDR irradiation, the response of quiescent cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for 5-bromo-2′-deoxyuridine. The response of the total (proliferating plus quiescent) tumor cells was determined from the 5-bromo-2′-deoxyuridine nontreated tumors. Results The difference in radiosensitivity between the total and quiescent cell populations after γ-ray irradiation was markedly reduced with reactor neutron beams or accelerated carbon ion beams, especially with a greater linear energy transfer (LET) value. Clearer repair in quiescent cells than in total cells through delayed assay or a decrease in the dose rate with γ-ray irradiation was efficiently inhibited with carbon ion beams, especially with a greater LET. With RDR irradiation, the radiosensitivity to accelerated carbon ion beams with a greater LET was almost similar to that to reactor thermal and epithermal neutron beams. Conclusion In terms of tumor cell-killing effect as a whole, including quiescent cells, accelerated carbon ion beams, especially with greater LET values, are very useful for suppressing the dependency on the heterogeneity within solid tumors, as well as depositing the radiation dose precisely.