The effect of deoxycoformycin and deoxyadenosine on deoxyribonucleotide concentrations in leukaemic cells.
Intracellular deoxynucleoside triphosphate pools of normal bone marrow, thymocytes and cells from patients with ALL and AML 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 significant rise of dATP concentrations in all groups (the highest rises occurring in the leukaemic groups particularly in AML and Thy-ALL). The concentrations of the other three 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 leukaemias.
D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D003070:Coformycin / Q000031:analogs & derivatives / Q000494:pharmacology*; D003838:Deoxyadenine Nucleotides / Q000378:metabolism; D003839:Deoxyadenosines / Q000494:pharmacology*; D003854:Deoxyribonucleotides / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology; D007945:Leukemia, Lymphoid / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism; D015649:Pentostatin; D012263:Ribonucleosides / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000378:metabolism
D003838:Deoxyadenine Nucleotides; D003839:Deoxyadenosines; D003854:Deoxyribonucleotides; D012263:Ribonucleosides; D003070:Coformycin; D015649:Pentostatin; C026600:2'-deoxyadenosine triphosphate