The effects of deoxycoformycin and deoxyadenosine on deoxyribonucleotide concentrations in leukaemic cells

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Abstract
Intracellular deoxynucleoside triphosphate pools of normal bone marrow, thymocytes and cells from patients with ALL [acute lymphoblastic leukemia] and AML [acute myelocytic leukemia] were measured after 2 h incubation with deoxycoformycin (dCF) 10-5 M and deoxyadenosine (AdR) 10-4 M in vitro and after another 30 min incubation in the absence of dCF and AdR (''chase'' experiment). Incubation with dCF and AdR resulted in a singificant rise of dATP concentrations in all groups (the highest rises ocurring in the leukemic groups particularly in AML and Thy-ALL). The concentrations of the other 3 deoxyribonucleoside triphosphates fell in all groups. The dATP level fell during the ''chase'' period but in Thy-ALL and thymocytes this fall was insignificant and slower than in the other groups. This suggests that not only intracellular build-up of dATP but also the capacity of the cell to degrade dATP is important for in vivo cytotoxicity of dCF treatment. These results help to explain the differences in response to dCF of the different leukemias.