Activation of deoxycytidine kinase by various nucleoside analogues.
The effect of different nucleoside analogues on deoxycytidine kinase (dCK) and thymidine kinase (TK) was compared in normal human lymphocytes and various leukemic cell lines. G-phase enriched tonsilar lymphocyte subpopulation treated by CdA showed more profound stimulation of dCK activity than S-phase cells. No substantial changes in TK activity were detected. CdA treatment increased the activity of dCK 4-fold in peripheral blood mononuclear cells (PBMC) and 2-fold in promyelocytic cell line HL60, too. However, no significant stimulation was detected either in CCRF-CEM or in K562 cell lines. 2-Cl-2'deoxy-2'F-adenine arabinoside (CAFdA), 2F-adenine arabinoside (F-araA) and cytosine arabinoside (AraC) had the same effect as CdA, although higher concentrations were needed for maximal activation. In contrast, treatment by dCyd caused slight inhibition of dCK. The possibility of interference of nucleoside analogues with the mechanisms of posttranslational modification of dCK was proposed.
Spasokoukotskaja
T
T
Semmelweis University of Medicine, Department of Medical Chemistry, Molecular Biology, and Pathobiochemistry, Budapest, Hungary.
Sasvári-Székely
M
M
Hullán
L
L
Albertioni
F
F
Eriksson
S
S
Staub
M
M
D000227:Adenine Nucleotides; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001087:Arabinonucleosides / Q000494:pharmacology*; D002453:Cell Cycle; D002478:Cells, Cultured; D017338:Cladribine / Q000494:pharmacology*; D000077866:Clofarabine; D003561:Cytarabine / Q000494:pharmacology*; D003842:Deoxycytidine Kinase / Q000378:metabolism*; D004789:Enzyme Activation; D018922:HL-60 Cells / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007938:Leukemia; D008214:Lymphocytes / Q000166:cytology / Q000201:enzymology*; D014066:Palatine Tonsil; D013937:Thymidine Kinase / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014740:Vidarabine / Q000494:pharmacology*
D000227:Adenine Nucleotides; D000964:Antimetabolites, Antineoplastic; D001087:Arabinonucleosides; D003561:Cytarabine; D017338:Cladribine; D000077866:Clofarabine; C105339:thymidine kinase 2; D013937:Thymidine Kinase; C092717:thymidine kinase 1; D003842:Deoxycytidine Kinase; D014740:Vidarabine