Deoxycytidine kinase can be also potentiated by the G-protein activator NaF in cells.

Recently, it has been shown, that 2-Chloro-deoxyadenosine (1), a series of analogues, and other DNA synthesis inhibitors, increased the deoxycytidine kinase (dCK) enzyme activity in different cells, without influencing thymidine kinase isoenzymes (TK1, TK2), dCMP-deaminase and thymidylate synthase (TS) activities (2,3). The dCK activity was 2-4 times higher in analogue treated cells, than in controls, which can not be explained by metabolic pool imbalance induced by the drugs. New mRNA and protein synthesis of dCK could not be detected, thus post-translational modification has been suggested for potentiation the activity of the dCK (1).

Human tonsillar lymphocytes as targets for immunosuppressive and anticancer drugs.

As has been shown earlier by us, the metabolism of extracellular deoxycytidine (dCyd) is 2-3 times higher in follicular and in PNA+ cells than in other cells. Deoxycytidine kinase (dCK) is one of the most important target enzymes for anti-proliferative drugs such as arabinosile-cytosine (ara-C), 2-Cl-deoxyadenosine (CdA). Neither the dCK activity nor the polypeptide correlates with the S phase of the cells, as thymidine kinase (TK1) does in tonsils.

Deoxyribocytidine is salvaged not only into DNA but also into phospholipid precursors. IV. Exogenous deoxyribocytidine can be used with the same efficacy as (ribo)cytidine for lipid activation.

Utilisation of exogenous (ribo)cytidine (3H-CR) and deoxyribocytidine (3H-CdR) for DNA/RNA synthesis and for activation of phospholipid intermediates was compared in human tonsillar lymphocytes. Incorporation of 3H-CdR into dCDP-choline and into dCDP-DAG was similar or even higher than labelling of CDP-choline and CDP-DAG from 3H-CR. No interconversion was found between CDP-DAG and dCDP-DAG, as shown by TLC separation of the ribo- and deoxyribocytidine derivatives.

The salvage of deoxycytidine into dCDP-diacylglycerol by macrophages and lymphocytes.

Extracellular deoxycytidine (CdR) was previously shown to be salvaged into water soluble [1] and also into lipidic [2] precursors of phospholipids in stimulated lymphocytes and in lymphoma cells [3]. In this paper we have described that non-dividing murine macrophages salvaged not only 5-3H-CdR but also tritiated thymidine (3H-TdR) mainly into the pools as nucleotides. Chlorpromazine shifted the CdR salvage into a lipidic compound of the cells which was identified as 3H-dCDP-diacylglycerol (dCDP-DAG).

Compartmentation of dCTP pools disappears after hydroxyurea or araC treatment in lymphocytes.

The calculated rate of DNA synthesis using [5-3H]TdR was about 4 times higher than in the case of [5-3H]CdR labeling, even after correction for the specific radioactivities of the intracellular pools. These data show a compartmentation of dCTP pools in lymphocytes. Hydroxyurea increased the specific activities of both dTTP and dCTP pools so that the calculated rate of DNA synthesis became equal.