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: Eric Van Den Neste, Caroline Smal, Sabine Cardoen, Anne Delacauw, Joëlle Frankard, Augustin Ferrant, Georges Van den Berghe, Françoise Bontemps
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 65 Issue 4 Pg. 573-80 (Feb 15 2003) ISSN: 0006-2952 [Print] England
• PMID: 12566084 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Suramin
• Deoxycytidine Kinase

Topics

• Antineoplastic Agents (pharmacology)
• B-Lymphocytes (drug effects, enzymology, radiation effects)
• DNA Repair (drug effects)
• Deoxycytidine Kinase (metabolism)
• Enzyme Activation (radiation effects)
• Humans
• Leukemia, Lymphocytic, Chronic, B-Cell (pathology)
• Suramin (pharmacology)
• Tumor Cells, Cultured
• Ultraviolet Rays