| Popis: |
Deoxycytidine kinase (dCK) and deaminase (dCDA) are as activating and inactivating enzymes, respectively, in the metabolism of several chemotherapeutically important deoxynucleoside analogues [1]. 2′2′-Difluorodeoxycytidine (dFdC; gemcitabine) has considerable antitumor activity against solid tumors, such as against the chemoresistant non-small cell lung cancer (NSCLC) and pancreatic cancer [2]. dCK catalyses the rate-limiting phosphorylation of CdR and its analogues to their corresponding monophos-phates [1,3]. To avoid an overestimation of the dCK activity by thymidine kinase 2 (TK2), which can also efficiently phosphorylate CdR [3], dCK activity was measured in the presence of thymidine (TdR) to inhibit TK2 [4]. dCDA inactivates cytidine (CR), CdR and its analogues to their deaminated products [5,6]. Previously we could not establish a relationship between antitumor activity and the dCK and dCDA activities [6], while in a cell line study more precise measurements of dCK showed a relation between sensitivity to dFdC and efficiency of dCK [7]. We now reevaluated the role of dCK, TK2 and dCDA in the antitumor effect of dFdC against different solid tumors. |
