title: Activation of deoxycytidine kinase by UV-C-irradiation in chronic lymphocytic leukemia B-lymphocytes.
abstract: Deoxycytidine kinase (dCK), a key enzyme of the deoxynucleoside salvage pathway, might have a preponderant role in DNA synthesis in resting chronic lymphocytic leukemia B-lymphocytes. In these cells, two important enzymes in deoxynucleoside triphosphate production, ribonucleotide reductase and thymidine kinase (TK), both cell-cycle regulated, are indeed very weakly expressed. This study investigated the regulation of dCK activity in response to UV-C light, a condition which causes DNA lesions and DNA repair synthesis. We observed that activity of dCK in B-CLL cells was upregulated up to 3-fold, 30 min after irradiation with 30 J/m(2) UV-C, whereas TK activity was unchanged. Activation of dCK by UV-C light was caused neither by a change in concentration of a low molecular weight metabolite nor by an increase in the amount of dCK protein. Activation of dCK by UV-C was mimicked by H(2)O(2), markedly counteracted by N-acetylcysteine, a general antioxidant, and completely abolished by the growth factor receptor inhibitor suramin. Taken together, these results indicate that dCK activity is upregulated by UV-C light through a postranslational modification that may be initiated at the cell surface through oxidative mechanisms. Suramin also suppressed the increase in DNA repair synthesis elicited by UV-C irradiation, suggesting that upregulation of dCK activity could contribute to the normal completion of DNA repair synthesis elicited by UV light.
authors.affiliation: Laboratory of Physiological Chemistry, Christian de Duve Institute of Cellular Pathology, Avenue Hippocrate 75, UCL-ICP 7539, B-1200 Brussels, Belgium. vandenneste@sang.ucl.ac.be
authors.forename: Eric
authors.initials: E
authors.lastname: Van Den Neste
authors.forename: Caroline
authors.initials: C
authors.lastname: Smal
authors.forename: Sabine
authors.initials: S
authors.lastname: Cardoen
authors.forename: Anne
authors.initials: A
authors.lastname: Delacauw
authors.forename: Joëlle
authors.initials: J
authors.lastname: Frankard
authors.forename: Augustin
authors.initials: A
authors.lastname: Ferrant
authors.forename: Georges
authors.initials: G
authors.lastname: Van den Berghe
authors.forename: Françoise
authors.initials: F
authors.lastname: Bontemps
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects*; D004260:DNA Repair / Q000187:drug effects; D003842:Deoxycytidine Kinase / Q000378:metabolism*; D004789:Enzyme Activation / Q000528:radiation effects; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D013498:Suramin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
chemical_list: D000970:Antineoplastic Agents; D013498:Suramin; D003842:Deoxycytidine Kinase