Cytotoxic effects of the hypoxic cell radiosensitizer Ro 7-0582 to tumor cells in vivo

The cytotoxicity of the nitroimidazole Ro 7-0582 to tumor cells has been studied in vivo using two transplantable tumors, the EMT6 tumor in BALB/c mice and the MDAH/MCa4 tumor in C3H mice. It was found that a high dose of Ro 7-0582 (1 mg/g) was toxic to approximately 90 percent of the tumor cells, that the toxicity only occurred when the tumor contained hypoxic cells, and that the toxicity was directed at both hypoxic and well-oxygenated cells. Also, there was little or no selective toxicity to irradiated, as opposed to unirradiated, tumor cells. The relative contributions of cytotoxicity and radiosensitization were evaluated in a tumor cure experiment for the MDAH/MCa4 tumor in C3H mice injected with 1 mg/g of Ro 7-0582. Calculations showed that in the absence of cytotoxicity the dose modification factor due to radiosensitization alone would have been 2.02 rather than the value of 2.30 observed. No toxicity was observed at the lower dose of 0.3 mg/g