Biological effect of intermittent radiation exposure in vivo: recovery from sublethal damage versus reoxygenation.

Purpose: In vivo effects of intermittent irradiation are influenced by recovery from sublethal damage (SLDR) and reoxygenation, so contribution of the two factors were investigated using murine tumors.
Methods and Materials: 1-cm-diameter SCCVII tumors growing in the legs of C3H/HeN mice were used. First, effects of 5 fractions of 6 Gy given at intervals of 2.5-15 min were compared using an in vivo-in vitro assay, by clamping the tumor-bearing legs to exclude the influence of reoxygenation. In the second and third experiments, changes in the hypoxic fraction at 0-15 min after 13 or 5 Gy were assessed by a paired cell survival method. Fourth, effects of 5 fractions of 5 Gy given at intervals of 3-10 min under conditions of limited reoxygenation were compared using a growth delay assay.
Results: Cell survival from clamped tumors tended to increase with elongation of the intervals, but not significantly. The hypoxic fraction tended to decrease at 5-15 min from the level immediately after irradiation. Effects on tumor growth tended to decrease with elongation of the intervals.
Conclusions: Reoxygenation occurring within 5-15 min appeared to compensate for SLDR in SCCVII tumors. When reoxygenation was limited, the decrease of radiation effect occurred due to SLDR.