Incubation of Chinese hamster ovary cells and KHT murine
fibrosarcoma tumor cells in the absence of
oxygen with 1-[2-14C]nitro-1-imidazolyl)-3-methoxy-
2-propanol, one of the most effective
radiation sensitizers of hypoxic cells, results in the preferential reduction of 1-[2-14C]nitro-1-imidazolyl)-3-methoxy-
2-propanol. The radioactivity associated with the
acid-insoluble precipitate from cells incubated in
nitrogen is about four times higher than that of cells incubated in air. When aqueous extracts of tissues of a C3H mouse bearing the KHT
tumor, after i.p. injection with 1-[2-14C]nitro-1-imidazolyl)-3-methoxy-
2-propanol, are analyzed, a reduction product is found in relatively higher yields in the
tumor than in normal tissues. The relative radioactivity in the pellet from the
tumor homogenate is also high in comparison with those of most normal tissues. These results provide suggestive evidence for a higher degree of hypoxic in the
tumor than in most normal tissues. The formation of reduction products and their subsequent binding to macromolecules may explain the preferential toxicity of
nitro compounds to mammalian cells under
hypoxia conditions. These results suggest that some
nitro compounds may be useful for the treatment of
tumors having a high fraction of hypoxic cells even in the absence of radiation.