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Differential cytotoxicity of deoxyguanosine and 8‐aminoguanosine for human leukemic cell lines and normal bone marrow progenitor cells
Author(s) -
De Fouw Nanneke J.,
Ma David D. F.,
Michalevicz Rita,
Gray Douglas A.,
Hoffbrand A. Victor
Publication year - 1984
Publication title -
hematological oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 44
eISSN - 1099-1069
pISSN - 0278-0232
DOI - 10.1002/hon.2900020208
Subject(s) - bone marrow , adenosine deaminase , progenitor cell , purine nucleoside phosphorylase , cytotoxicity , microbiology and biotechnology , cell culture , leukemia , cancer research , clonogenic assay , chemistry , in vitro , immunology , stem cell , medicine , adenosine , biology , biochemistry , purine , enzyme , genetics
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 (100μ m ) alone did not have any inhibitory effect, but when used with GdR (2·5 × 10 −5 m ) a synergistic effect was seen towards T cells. Incubation with GdR and AG resulted in a marked decrease in cell viability (> 90 per cent in three and > 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.