Partial hypoxia as a cause of radioresistance in a human tumor xenograft: its influence illustrated by the sensitizing effect of misonidazole and hyperbaric oxygen.

While previous studies with three human tumor xenografts suggest that contact-resistance plays a major role in the response of these tumors to radiation, it remains possible that partial hypoxia may provide an alternate explanation. The present study was carried out to check this possibility by investigating the influence of misonidazole (MISO) and hyperbaric oxygen (HBO) on both the initial and distal components of the survival curves of HRT18 tumor cells. The effect of a challenge dose of radiation on the initial radioresistance of this tumor was also studied. To assess the effects of MISO and HBO, tumor cell survival was determined by excision assay in two groups of tumor-bearing mice, one given MISO (1 mg/g body weight, i.p.) 45 min before irradiation and the other exposed to HBO (3.5 bars). MISO treatment caused greater sensitization than HBO. The enhancement ratios at the 5.10(-1) level were 1.7 (MISO) and 1.7 (HBO); at the 10(-1) level, they were 1.6 (MISO) and 1.4 (HBO); while at 10(-2), they were 1.6 (MISO) and 1.4 (HBO). These two sensitizing effects favor the hypothesis that solid tumors contain a compartment of partially hypoxic cells. To study the effect of a challenge radiation dose on initial radioresistance, tumors were given a challenge dose of 8 Gy, followed 24-48 hr later by doses ranging from 2-12 Gy. The challenge dose did not modify the shape of the survival curve.