Abstract
In vitro cytotoxicity of various purine nucleosides and purine enzyme inhibitors, alone or in combination, and of the alkylating agent mafosfamide incubated for 4/ 24h has been studied in 17 leukaemic cell lines of various phenotypes and normal bone marrow cells. The purine nucleosides/inhibitors included: 2′chlorodeoxyadenosine (CdAdo), 2′deoxyadenosine (dAdo), 3′deoxyadenosine (3′dAdo), adenosine, adenine arabinoside (ara-A), deoxyguanosine (dGdo), guanine arabinoside (Ara-G), 2-deoxycoformycin (dCF) and 8-aminoguanosine (8-AG). T-lymphoblastic cell lines were found to be the most sensitive to the toxic effects of the purine analogues. Marked and selective inhibition of T-cell growth was shown by the combinations dCF with either dAdo or ara-A, of 8-AG with dGdo and by CdAdo or Ara-G alone. These compounds even at high concentrations produced only partial inhibition of the growth of normal bone marrow cells in in vitro assays (CFU-GM and CFU-GEHM) except for CdAdo which inhibited the formation of CFU-GEMM colonies. dCF plus 3′dAdo was toxic to all the cell lines at the concentrations employed, as well as to CFU-GM and CFU-GEMM and so was mafosfamide. The high therapeutic index of some of the purine nucleosides after a relatively short exposure period makes them candidates for selective in vitro removal of residual neoplastic cells in autologous BMT for acute lymphoblastic leukaemia of T-cell origin.
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Piga, A., Ganeshaguru, K., Sarah Green, E. et al. 39 SELECTIVE TOXICITY OF PURINE NUCLEOSIDES TO HUMAN T-LEUKAEMIC CELLS. Pediatr Res 24, 117 (1988). https://doi.org/10.1203/00006450-198807000-00063
Issue Date:
DOI: https://doi.org/10.1203/00006450-198807000-00063