Differential cytotoxicity of deoxyguanosine and 8-aminoguanosine for human leukemic cell lines and normal bone marrow progenitor cells.
The inhibitory effect of deoxyguanosine (GdR) alone or in combination with the purine nucleoside phosphorylase (PNP) inhibitor, 8-aminoguanosine (AG) was tested on human T, B, cALL and myeloid leukaemia cell lines and on normal human bone marrow haemopoietic progenitor cells. GdR was found to be toxic to T-leukaemia cells. AG (100 microM) alone did not have any inhibitory effect, but when used with GdR (2.5 X 10(-5)M) a synergistic effect was seen towards T cells. Incubation with GdR and AG resulted in a marked decrease in cell viability (greater than 90 per cent in three and greater than 75 per cent in four of 5 T leukaemic cell lines tested at 72 h). This drug combination did not inhibit the growth of non-T leukaemic cells and was also non-toxic to normal bone marrow multipotent progenitor cells (CFU-GEMM) in vitro. Adenosine deaminase (ADA) acts consecutively with PNP in purine degradation. The addition of an ADA inhibitor, deoxycoformycin and deoxyadenosine, however, did not enhance the toxicity of GdR and AG for T cell leukaemia. The possibility of using GdR and AG for in vitro removal of residual T leukaemic blasts with the sparing of normal bone marrow cells, prior to autologous bone marrow transplantation should be further explored.
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay; D004261:DNA Replication / Q000187:drug effects; D003849:Deoxyguanosine / Q000633:toxicity*; D006151:Guanosine / Q000031:analogs & derivatives* / Q000633:toxicity; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007700:Kinetics; D007938:Leukemia / Q000503:physiopathology*; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors
D006151:Guanosine; C032533:8-aminoguanosine; D011683:Purine-Nucleoside Phosphorylase; D003849:Deoxyguanosine