Analysis of radio-sensitivity and recovery from radiation-induced damage following heavy-ion beam irradiation in comparison with gamma-ray irradiation, referring to the effect on intratumor quiescent cells.

Abstract

Purpose: We clarified the radiobiological characteristics of irradiation with 290 MeV/u carbon ions versus gamma-rays based on the responses of quiescent and total tumor cell populations in vivo. Materials/Methods: SCC VII tumor-bearing mice received a continuous administration of BrdU to label all intratumor proliferating (P) cells. Then, they received 290 MeV/u carbon ions or gamma-rays. Right after irradiation, some of them further received intratumor acutely hypoxic fraction-releasing agent nicotinamide (NA) or cramping the tumor-bearing thighs to induce total hypoxia inside the tumors. Immediately or 9-12 hours after the irradiation, the tumors were isolated and incubated with a cytokinesis blocker, and the micronucleus (MN) frequency in cells without BrdU labeling (= Q cells) was determined using immunofluorescence staining for BrdU. The MN frequency in the total (= P+Q) tumor cell population was determined using tumors that were not pretreated with BrdU. Results: The difference in radiosensitivity between total and Q cell populations was markedly reduced with carbon ion beams, especially those with a higher LET value. PLDR by Q cells was efficiently inhibited with the carbon ion beams, again especially with a higher LET value. Carbon ion beam irradiation with a higher LET value could efficiently reduce the dependency of radiosensitivity on the heterogeneity in solid tumors. NA enhanced PLDR and cramping tumor-bearing thighs inhibited PLDR, especially markedly in (P+Q) cells after gamma-ray irradiation.