Modulation of human deoxycytidine kinase activity as a response to cellular stress induced by NaF

Deoxycytidine kinase (dCK) is one of the key enzymes of deoxynucleoside sal vage supplying resting lymphocytes with DNA precursors for synthesis and re pair. The level of dCK activity is especially important in chemotherapy wit h the use of deoxynucleoside analogues like arabinosyl cytosine (Citarabid, ara-C), or 2-chloro-deoxyadenosine (Cladribine, CdA). Previous results sho wed that Cladribine treatment of human lymphocytes increased several fold t he activity of dCK without increasing the amount of dCK protein itself (Sas vari-Szekely, et al., 1998, Biochem. Pharmacol. 56, 1175), and a possible p ost-translational modification was suggested. This theory was further inves tigated using NaF as an inhibitor of protein phosphatases. It was shown tha t NaF treatment of cells elevated dCK activity while inhibiting DNA synthes is. The possible mechanism of dCK activation/inactivation induced by exposu re of cell cultures to different agents is discussed.