The influence of irradiation of the tumor bed on tumor hypoxia: measurements by radiation response, oxygen electrodes, and nitroimidazole binding.

SCCVII carcinomas and RIF-1 sarcomas were transplanted and grown in the unirradiated (control tumors) or preirradiated tissue of mice. Tumor oxygenation was measured when the tumors were in the size range 50-150 mm3 using three different methods. The tumors growing in tissues preirradiated with 20 Gy were significantly more hypoxic than the control tumors for both tumor types. Radiobiologically hypoxic fractions of these tumors were approximately 10 times higher than those of the controls. The relative [3H]misonidazole binding of the tumors transplanted into irradiated tissue was approximately five times (P < 0.01) higher in SCCVII tumors or approximately two times (P < 0.05) higher in RIF-1 tumors than that of the controls. The pO2 histographs measured directly by a polarographic microelectrode were more hypoxic (P < 0.001) and changed from bimodal to unimodal in pattern in the tumors transplanted into irradiated tissue compared to those of the controls. The increase of the relative [3H]misonidazole binding in the tumors transplanted into irradiated tissue compared to that of the controls was similar to the increase of the cumulative frequency of pO2 below 10.0 mm Hg for both the SCCVII and the RIF-1 tumors. The data suggest that the majority of tumor cells with pO2 values below 5.0 mm Hg were clonogenic in the SCCVII tumors while only a small portion of tumor cells with pO2 below 5.0 mm Hg were clonogenic in the control RIF-1 tumors. Increased hypoxia caused by preirradiation of the tumor bed is a useful model in evaluating the efficacy of various treatments affected by tumor oxygenation levels. The model is also useful in evaluating techniques for measuring oxygen levels.