Activation of deoxycytidine kinase during inhibition of DNA synthesis by 2-chloro-2'-deoxyadenosine (cladribine) in human lymphocytes

Mária Sasvári-Székely, Tatjana Spasokoukotskaja, Melinda Szóke, Zsolt Csapó, Ágnes Turi, Ildikó Szántó, Staffan Eriksson, Mária Staub

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Abstract

Deoxycytidine kinase (dCK, EC.2.7.1.74), a key enzyme in intracellular metabolism of many antileukemic drugs, was shown to be activated during treatment of lymphocytes by 2-chloro-2'-deoxyadenosine (Cl-dAdo, cladribine), a potent inhibitor of DNA synthesis. While 5-[3H]-thymidine (TdR) incorporation into DNA was decreased by 80-90%, dCK activity was doubled as a consequence of incubating the cells with 1 μM 2-chloro-2'-deoxyadenosine. Thymidine kinase (dTK, EC.2.7.1.21) activity was slightly decreased under the same conditions, similarly to 5-[3H]-thymidine incorporation. dCK activation could not be prevented by cycloheximide, and neither the amount of dCK protein nor its mRNA level was increased after 2-chloro-2'-deoxyadenosine treatment. These results suggest a post-translational activation of dCK protein during inhibition of DNA synthesis. Copyright (C) 1998 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)1175-1179
Number of pages5
JournalBiochemical Pharmacology
Volume56
Issue number9
DOIs
Publication statusPublished - Nov 1 1998

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Keywords

  • 2-chloro-2'-deoxyadenosine
  • Cladribine
  • Deoxycytidine kinase
  • Human
  • Lymphocyte
  • Thymidine kinase

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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