The effect of post-irradiation tumor oxygenation status on recovery from radiation-induced damage in vivo: With reference to that in quiescent cell populations

Purpose To elucidate the effect of tumor oxygenation status on recovery from damage following γ-ray or accelerated carbon ion irradiation in vivo, including in quiescent (Q) cells. Methods SCC VII tumor-bearing mice were continuously given 5-bromo-2′-deoxyuridine (BrdU) to label all proliferating (P) cells. They received γ-ray or accelerated carbon ion irradiation with or without tumor clamping for inducing hypoxia. Immediately after irradiation, cells from some tumors were isolated, or acute hypoxia-releasing nicotinamide was loaded to the tumor-bearing mice. For 9 h after irradiation, some tumors were kept aerobic or hypoxic. Then isolated tumor cells were incubated with a cytokinesis blocker. The response 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 BrdU non-treated tumors. Results Clearer recovery in Q cells than total cells and after aerobic than hypoxic γ-ray irradiation was efficiently suppressed with carbon ion beams. Inhibition of recovery through keeping irradiated tumors hypoxic after irradiation and promotion of recovery by nicotinamide loading were observed more clearly with γ-rays, after aerobic irradiation and in total cells than with carbon ion beams, after hypoxic irradiation and in Q cells, respectively. Conclusions Tumor oxygenation status following irradiation can manipulate recovery from radiation-induced damage, especially after aerobic γ-ray irradiation in total cells. Carbon ion beams are promising because of their efficient suppression of the recovery.