Antitumor activity of the 3'-chloroethylnitrosourea analog of thymidine and the prevention by co-administered thymidine of lethality but not of anticancer activity.
The effect of the 3'-nitrosourea analog of thymidine (3'-[3-(2-chloroethyl)-3-nitrosoureido]-3'-deoxythymidine; 3'-CTNU) on the growth of the murine L1210 and P388 leukemias in mice was investigated. A single injection of 3'-CTNU (40 mg/kg) was minimally toxic to mice bearing the L1210 leukemia and produced 60-day survivors. The coadministration of thymidine did not prevent the initial loss of weight caused by 3'-CTNU but did prevent the lethality otherwise produced in non-tumor-bearing mice. A single dose of thymidine (2 g/kg) administered to L1210-bearing mice had no anticancer activity and when coadministered with 3'-CTNU had no detrimental effect on the potent antitumor effects of 3'-CTNU. Similar results were obtained against P388 leukemia. The hematopoietic toxicity produced by the administration of 3'-CTNU to non-tumor-bearing mice, as evidenced by changes in the white blood cells, neutrophil, and agar diffusion chamber precursor cell concentrations in the hematocrit and in bone marrow cellularity, could not be prevented by thymidine. Therefore, the lethality produced by 3'-CTNU is probably not related to hematopoietic toxicity since the coadministration of thymidine completely prevented any lethality.
D000818:Animals; D000970:Antineoplastic Agents; D001835:Body Weight; D001853:Bone Marrow / Q000187:drug effects; D015224:Dideoxynucleosides; D004347:Drug Interactions; D005260:Female; D006400:Hematocrit; D006410:Hematopoiesis / Q000187:drug effects; D006413:Hematopoietic System / Q000187:drug effects; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000473:pathology; D007941:Leukemia P388 / Q000188:drug therapy* / Q000473:pathology; D007942:Leukemia, Experimental / Q000188:drug therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D009607:Nitrosourea Compounds / Q000494:pharmacology* / Q000633:toxicity; D013936:Thymidine / Q000494:pharmacology*
D000970:Antineoplastic Agents; D015224:Dideoxynucleosides; D009607:Nitrosourea Compounds; C027799:3'-(3-(2-chloroethyl)-3-nitrosourea)-3'-deoxythymidine; D013936:Thymidine