Tumor bed effect-induced reduction of tumor radiocurability through the increase in hypoxic cell fraction

Two murine tumors, designated FSA and SA-NH, that exhibit strong tumor bed effect (TBE), were found to be less radiocurable if they grew in the preirradiated s.c. tissue. Tumors were transplanted into the right thighs irradiated with 30 Gy one day earlier, and were irradiated when they grew to 6 mm. The TBE-caused reduction in tumor radiocurability was manifested by the increase in TCD50 values. Tumor irradiation under hypoxic conditions increased TCD50 values less, and the hypoxic cell radiosensitizer misonidazole reduced TCD50 values more, when tumors grew in preirradiated than when they grew in unirradiated legs. This implies that TBE-induced increase in TCD50 was due to increase in hypoxic fraction of tumor cells. For 6 mm SA-NH tumor the estimated increase in hypoxic cell fraction was from the control value of 3% to 12%. Thus, TBE causes the reduction in tumor radiocurability through the increase in hypoxic fraction of tumor cells.