Determinants in chemosensitivity of oncogene-transformed NIH3T3 cells to 2'-C-cyano-2'-deoxy-1-beta-D-arabinofuranosylcytosine.

2'-C-Cyano-2'-deoxy-1-beta-D-arabinofuranosylcytosine (CNDAC) is a novel 2'-deoxycytidine (dCyd) analogue with potent antitumor activity. To elucidate the determinants of chemosensitivity to CNDAC, the intracellular accumulation of CNDAC and the activities of dCyd kinase and cytidine deaminase were investigated in transformed NIH 3T3 cells with different genetic bases. The results indicate that the primary determinants of chemosensitivity to CNDAC are different in each cell type, but membrane transportation and the enzyme activities of dCyd kinase and cytidine deaminase are critical factors underlying the antitumor action of CNDAC. Moreover, the expression or function of these factors appears to be influenced by the activation of various oncogenes.