Toxicity and radiation protective effect of WR-77913 in BALB/c mice.
The toxicity and radiation protective effect obtained by intraperitoneal injection of WR-77913 have been investigated in BALB/c mice. The toxic LD50/30 was 3574 mg/kg. When WR-77913 was given 30 min before whole body irradiation adequate protection was observed against bone marrow and gut death. Dose modifying factors of 1.91 and 1.76 for bone marrow and 1.95 and 1.80 for gut death were obtained with drug doses roughly equivalent to one half and one quarter of the maximum tolerable doses (MTD). No protective effect was observed against central nervous system injury. Preliminary experiments with the EMT6 tumor show limited tumor protection with a dose of WR-77913 equivalent to 70 per cent of the MTD. Because of its low toxicity, adequate bone marrow and gut protection at doses equivalent to one quarter MTD and limited protection of the EMT6 tumor, WR-77913 deserves further investigation to determine its value in multiple drug dose regimens and its capability to protect other normal tissues.
D004999:Amifostine / Q000031:analogs & derivatives / Q000633:toxicity*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology / Q000532:radiotherapy; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D011833:Radiation Injuries, Experimental / Q000209:etiology; D011837:Radiation-Protective Agents; D011878:Radiotherapy / Q000379:methods*; D014916:Whole-Body Irradiation
D009946:Organothiophosphorus Compounds; D011837:Radiation-Protective Agents; C035284:WR 77913; D004999:Amifostine