Enhancement of CCNU cytotoxicity by misonidazole: possible therapeutic gain.
Enhancement of CCNU cytotoxicity by misonidazole (MISO) was studied in three tumours and two normal tissues in the mouse. The 3 experimental tumours (SCCVII/St, EMT6 and KHT) showed very different sensitivities to CCNU alone, but MISO enhanced the cell killing in ech case. The effect was not always dose-modifying, so that the CCNU dose range for the greatest enhancement was different in each of the tumours. In all 3 tumours, enhancement increased with dose of MISO. The effect on two normal tissues, marrow (CFU-S) and testis (spermatogonia), was also investigated. Enhancement of marrow toxicity could be demonstrated only at CCNU doses greater than 12.5 mg/kg, so that at lower CCNU doses there was a therapeutic gain equal to the tumour enhancement ratio. The spermatogonia effect, however, showed enhancement by MISO similar to that seen in the tumours at all CCNU doses up to 20 mg/kg.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D008130:Lomustine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008920:Misonidazole / Q000494:pharmacology*; D009374:Neoplasms, Experimental / Q000473:pathology*; D009593:Nitroimidazoles / Q000494:pharmacology*; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D013093:Spermatogonia / Q000187:drug effects; D013997:Time Factors
D009593:Nitroimidazoles; D009607:Nitrosourea Compounds; D008130:Lomustine; D008920:Misonidazole