We sought to reduce tumor hypoxia by topical application of a vasodilator, benzyl nicotinate (BN), and investigated its effect on the growth of tumors irradiated at times when tumor pO2 increased. EPR oximetry was used to follow the changes in the tissue pO2 of subcutaneous radiation-induced fibrosarcoma (RIF-1) tumors during topical applications of 1.25–8% BN formulations for 5 consecutive days. The RIF-1 tumors were hypoxic with a tissue pO2 of 4.6–7.0 mmHg. A significant increase in tumor pO2 occurred 10–30 min after BN application. The formulation with the minimal BN concentration that produced a significant increase in tumor pO2 was used for the radiation study. The tumors were irradiated (4 Gy × 5) at the time of the maximum increase in pO2 observed with the 2.5% BN formulation. The tumors with an increase in pO2 of greater than 2 mmHg from the baseline after application of BN on day 1 had a significant growth inhibition compared to the tumors with an increase in pO2 of less than 2 mmHg. The results indicate that the irradiation of tumors at the time of an increase in pO2 after the topical application of the 2.5% BN formulation led to a significant growth inhibition. EPR oximetry provided dynamic information on the changes in tumor pO2, which could be used to identify responders and non-responders and schedule therapy during the experiments.
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Vol. 173 • No. 5