Radioprotection combined with hypoxic sensitization during radiotherapy of a solid murine tumor.
EMT6 tumors were transplanted intramuscularly in the right hind leg of female BALB/c mice and irradiated when they reached a diameter of 6-7 mm. Each mouse received an intraperitoneal injection of WR-2721, misonidazole, or both prior to irradiation, and the dose needed to control half of the tumors at 30 days (TCD50/30) was recorded. WR-2721 offered slight tumor protection, with a dose-modifying factor (DMF) of 1.04-1.15 for radioprotector doses of 150-500 mg/kg. Pretreatment with misonidazole at doses of 300-900 mg/kg yielded tumor sensitization with a DMF of 0.71-0.92. Pretreatment with both WR-2721 and misonidazole gave overall tumor sensitization with a DMF of 0.78-0.97. Possible combinations of sensitizers and protectors, while providing overall tumor sensitization, do not seem to improve the therapeutic ratio over what could be obtained from a sensitizer or protector alone.
D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008920:Misonidazole / Q000494:pharmacology*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology / Q000532:radiotherapy*; D009593:Nitroimidazoles / Q000494:pharmacology*; D009946:Organothiophosphorus Compounds / Q000494:pharmacology*; D010100:Oxygen; D011879:Radiotherapy Dosage; D013223:Statistics as Topic
D009593:Nitroimidazoles; D009946:Organothiophosphorus Compounds; D008920:Misonidazole; D004999:Amifostine; D010100:Oxygen