The sensitizer adduct technique [( 3H]
misonidazole binding) was used to assess the extent of murine bone marrow
hypoxia following treatment with a variety of radioprotectors. The binding rates previously determined in vivo were compared to those obtained by incubating marrow cells in atmospheres of varying
oxygen content. Parallel experiments demonstrated that the
oxygen dependence of [3H]
misonidazole binding (Km approximately 0.15%
oxygen) was similar to the
oxygen dependence of marrow radiosensitivity (Km approximately 0.2%
oxygen). Maximally radioprotective doses of several drugs have been shown to increase the binding of [3H]
misonidazole significantly in vivo. A comparison to the in vitro binding rates suggests that the average
oxygen concentration in the marrow at times associated with radioprotection was on the order of 0.5 to 0.8%
oxygen. The relative importance of marrow
hypoxia to the overall radioprotective effects of different drugs may vary considerably. However, these results have demonstrated that certain
radioprotective drugs can induce marrow
hypoxia and this reduced pO2 may contribute to the efficacy of these agents.