Enhancement of the effect of cytotoxic drugs by radiosensitizers.
Misonidazole (MISO) potentiates the action of cyclophosphamide (CY) and melphalan in the WHFIB culture-adapted fibrosarcoma, whether assayed by cell survival or tumour-growth delay. In the case of CY, MISO also inhibited recovery from potentially lethal drug damage. The optimum effect was seen when MISO was given 1 h before CY, though it was also effective when given 6 h before or 1 h after the drug. Other radiosensitizers also potentiated the action of CY. There was only a small effect of MISO on the LD50 of CY and no effect on CY toxicity as assayed by changes in blood counts or damage to bladder epithelium. However, mice bearing multiple lung tumours were less able to cope with the combined treatment than those bearing s.c. tumours.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003520:Cyclophosphamide / Q000627:therapeutic use* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005354:Fibrosarcoma / Q000188:drug therapy; D066298:In Vitro Techniques; D008558:Melphalan / Q000627:therapeutic use*; D051379:Mice; D008920:Misonidazole / Q000627:therapeutic use*; D009593:Nitroimidazoles / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D012513:Sarcoma, Experimental / Q000188:drug therapy; D014554:Urination / Q000187:drug effects
D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D008920:Misonidazole; D003520:Cyclophosphamide; D008558:Melphalan