Radiosensitizing and toxic effects of the 2-nitroimidazole Ro-07-0582 in hypoxic mammalian cells

The properties of the electron-affinic 2-nitroimidazole Ro-07-0582 have been examined in vitro in two Chinese hamster cell lines, CHO and CH2B2. The drug was found to sensitize 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 is also shown to have a chemotherapeutic potential in that it demonstrates a very selective toxicity for hypoxic cells after a few hours 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 exercized in the clinical application of Ro-07-0582 to avoid possible injury to normal hypoxic tissues in the body