Activation of deoxycytidine kinase by gamma-irradiation and inactivation by hyperosmotic shock in human lymphocytes

Z. Csapó, Gergely Keszler, G. Sáfrány, T. Spasokoukotskaja, Iannis Talianidis, M. Staub, M. Sasvári

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Deoxycytidine kinase (dCK) is a key enzyme in the intracellular metabolism of deoxynucleosides and their analogues, phosphorylating a wide range of drugs used in the chemotherapy of leukaemia and solid tumours. Previously, we found that activity of dCK can be enhanced by incubating primary cultures of lymphocytes with substrate analogues of the enzyme, as well as with various genotoxic agents. Here we present evidence that exposure of human lymphocytes to 0.5-2Gy dosage of γ-radiation as well as incubation of cells with calyculin A, a potent inhibitor of protein phosphatase 1 and 2A, both elevate dCK activity without changing the level of dCK protein. When cells were gamma-irradiated in the presence of calyculin A, a more pronounced activation of dCK was observed. In contrast, both basal and stimulated dCK activities were reduced by hyperosmotic treatment of the cells. DNA repair determined by the Comet assay and by thymidine incorporation was induced by irradiation. Complete repair of γ-irradiated DNA was detected within 1hr following the irradiation along with dCK activation, but the rate of repair was not accelerated by calyculin A. These data provide evidence for the activation of dCK upon DNA damage and repair that seems to be mediated by phosphorylation of the enzyme, suggesting the role of dCK in DNA repair processes.

Original languageEnglish
Pages (from-to)2031-2039
Number of pages9
JournalBiochemical Pharmacology
Volume65
Issue number12
DOIs
Publication statusPublished - Jun 15 2003

Fingerprint

Deoxycytidine Kinase
Lymphocytes
Shock
Chemical activation
Irradiation
Repair
DNA Repair
DNA
Enzymes
Cells
Radiation Dosage
Protein Phosphatase 2
Phosphorylation
Comet Assay
Chemotherapy
Cell culture
Metabolism
Thymidine
DNA Damage
Tumors

Keywords

  • γ-Irradiation
  • Calyculin A
  • Deoxycytidine kinase
  • DNA repair
  • Enzyme activation
  • Nucleotide metabolism

ASJC Scopus subject areas

  • Pharmacology

Cite this

Activation of deoxycytidine kinase by gamma-irradiation and inactivation by hyperosmotic shock in human lymphocytes. / Csapó, Z.; Keszler, Gergely; Sáfrány, G.; Spasokoukotskaja, T.; Talianidis, Iannis; Staub, M.; Sasvári, M.

In: Biochemical Pharmacology, Vol. 65, No. 12, 15.06.2003, p. 2031-2039.

Research output: Contribution to journalArticle

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