Cytotoxic and radiosensitizing effects of hypoxic cell sensitizers on EMT6 mouse mammary tumour cells in vivo and in vitro.

The radiosensitizing activities and toxicities of misonidazole, metronidazole, 2-Methythio-3-nitropyrrole (3NPR), 2-amino-5-nitrothiazole (ANT) and 2,5-dinitroimidazole (KA121) were studied using EMT6 tumour cells and BALB/c KaRw mice. For 10(-4)M concentrations of the drugs, the DMF's for hypoxic cells were: Misonidazole, 1.6; 3NPR, 1.5, ANT, 1.5; KA121, 1.8. The OER was 3.2. In general, the drugs were toxic to hypoxic cells and were not toxic to aerobic cells at 10(-3)M for 24 h. The LD50's in BALB/c KaRw mice were: misonidazole, 1500 mg/kg; 3NPR, 350 mg/kg ANT, 420 mg/kg. In vivo, 1 mg/g misonidazole or metronidazole reduced the terminal slope of the tumour cell survival curve by a factor of 2.2 or 1.6 respectively.