title: CB 1954 revisited. II. Toxicity and antitumour activity.
abstract: We have assessed the antitumour activity of the nitrophenylaziridine CB 1954 in vitro and in vivo. For EMT6 mouse mammary tumour multicellular spheroids under hypoxic conditions in vitro, a 6-h exposure to 40 micrograms/ml reduced the surviving fraction to as low as 10(-3) and the growth delay was 5.4 days. Oxic cells were twofold less sensitive. Phenyl AIC protected oxic and hypoxic cells equally. Under oxic conditions minimal cell killing was seen with HT29 cells, either in multicellular spheroids or in monolayer; a 6-h exposure to 40 micrograms/ml gave a spheroid growth delay of 1.5-1.7 days. No growth delay was seen with single maximum tolerated doses of CB 1954 against HT29 grown as a xenograft in immunosuppressed mice. Only minimal growth delays of 1-2 days were seen with similar doses against the EMT6 tumour and the RIF-1 and KHT sarcomas in mice. Little activity was seen with maximum tolerated doses given once a day for 5 days against EMT6 and RIF-1. No chemosensitization was measurable with CCNU, cyclophosphamide or melphalan in the KHT tumour.
mesh_terms: D000818:Animals; D001388:Aziridines / Q000627:therapeutic use* / Q000633:toxicity; D001389:Azirines / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D008130:Lomustine / Q000627:therapeutic use; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D008558:Melphalan / Q000627:therapeutic use; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D012513:Sarcoma, Experimental / Q000188:drug therapy
chemical_list: D001388:Aziridines; D001389:Azirines; C100099:tretazicar; D008130:Lomustine; D003520:Cyclophosphamide; D008558:Melphalan