Activation of deoxycytidine kinase by UV-C-irradiation in chronic lymphocytic leukemia B-lymphocytes.

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作者：

EVD Neste，C Smal，S Cardoen，A Delacauw，J Frankard，A Ferrant，GVD Berghe，F Bontemps

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摘要：

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 2O 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.

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关键词：

CdA, 2-chloro-2′-deoxyadenosine CLL, chronic lymphocytic leukemia dCK, deoxycytidine kinase dCyd, deoxycytidine dNTP, deoxynucleoside triphosphate dThd, thymidine HU, hydroxyurea NAC, N-acetylcysteine TK, thymidine kinase