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.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D066298:In Vitro Techniques; D007928:Lethal Dose 50; D008325:Mammary Neoplasms, Experimental / Q000532:radiotherapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009593:Nitroimidazoles / Q000494:pharmacology* / Q000633:toxicity; D010100:Oxygen; D011758:Pyrroles / Q000494:pharmacology* / Q000633:toxicity; D011838:Radiation-Sensitizing Agents; D013844:Thiazoles / Q000494:pharmacology* / Q000633:toxicity
D009593:Nitroimidazoles; D011758:Pyrroles; D011838:Radiation-Sensitizing Agents; D013844:Thiazoles; D010100:Oxygen