The enhanced cytotoxicity of combinations of 1-beta-D-arabinofuranosylcytosine and methotrexate.
Although both 1-beta-D-arabinofuranosylcytosine (ara-C) and methotrexate are presumed to be toxic as a result of their interference with DNA synthesis, results obtained with L1210 cells in vivo suggest that the combination of ara-C and methotrexate is capable of killing cells by a mechanism not related simply to DNA synthesis inhibition. Simultaneous administration of ara-C and methotrexate, or administration of these two agents within a 10-hr interval, independent of order, produces a synergistic cell kill of L1210 cells but a less than additive effect on normal hematopoietic stem cells. The extent of synergy seems dependent upon the dose of ara-C.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003561:Cytarabine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D066298:In Vitro Techniques; D007700:Kinetics; D007939:Leukemia L1210; D008727:Methotrexate / Q000633:toxicity*; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D013154:Spleen / Q000166:cytology; D013997:Time Factors
D003561:Cytarabine; D008727:Methotrexate