Radiosensitizing and Toxic Effects of the 2-Nitroimidazole Ro-07-0582 in Hypoxic Mammalian Cells

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Abstract
The properties of the electron-affinic 2-nitroimidazole Ro-07-0582 were examined in vitro in 2 Chinese hamster cell lines, CHO [Chinese hamster ovary cells] and CH2B2 [embryonic cells]. The drug sensitized hypoxic cells to radiation damage selectively with a high efficiency. At concentrations greater than 10 mM the drug has a dose-modifying factor of approximately 3.0 in hypoxic cultures. It does not alter the response of aerobic cells. Pre- or postirradiation treatment of cells with Ro-07-0582 has little, if any, effect. At high cell concentrations, where many sensitizers are ineffective, this compound retains most of its radiosensitizing capability. Ro-07-0582 also has a chemotherapeutic potential in that it demonstrates a very selective toxicity for hypoxic cells after a few h of exposure. It is much less toxic to aerobic cells. This property, while it may serve as a useful complement to the radiosensitizing effect of the drug, suggests that care must be exercised in the clinical application of Ro-07-0582 to avoid possible injury to normal hypoxic tissues in the body.