Effects of mitomycin C alone and in combination with X-rays on EMT6 mouse mammary tumors in vivo.

The effects of mitomycin C alone and in combination with radiation on the cells of EMT6 mouse mammary tumors in BALB/cKaRw mice were examined. At doses near the toxic level, approximately 98% of the tumor cells were killed by a single injection of mitomycin C. Both proliferating and quiescent cells and both hypoxic and aerobic cells were killed by the drug. Cytotoxicity with mitomycin C occurred rapidly and was apparently complete within 30 minutes after injection of the drug . No evidence was found for repair of potentially lethal mitomycin C damage or sublethal mitomycin C damage by the tumor cells. Mitomycin C and radiation in combination produced an additive cytotoxicity; neither agent was found to alter significantly the shape of the dose-response curve for the other agent. The cytotoxicity of mitomycin C and radiation in combination depended on the sequence and timing of the treatments; additive toxicities were obtained when mitomycin C was given just after, just before, or up to 24 hours before irradiation, but the combination was less effective when mitomycin C was given 2-12 hours after irradiation.