Inhibition of intracellular pyrimidine ribonucleotide reduction by deoxycytidine, arabinosylcytosine and hydroxyurea

Abstract

A correlation has been made between the ability of selected agents to inhibit intracellular pyrimidine nucleotide reduction and the ability of these agents to inhibit the growth of L5178Y cells. Both deoxycytidine and its analogue, arabinosylcytosine, appeared to inhibit intracellular cytidine phosphate reduction. The depletion of deoxycytidine phosphate pools may play a role in arabinosylcytosine toxicity by enhancing the action of arabinosylcytosine at one or more of its proposed sites of action. Hydroxyurea inhibited uridine phosphate reduction, and this inhibition correlated well with the growth inhibition caused by this agent. The inability of hydroxyurea to affect cytidine phosphate reduction suggests that there may be a cytidine phosphate reductase present in L5178Y cells which either is insensitive to inhibition by hydroxyurea or is sequestered at an intracellular site which is relatively inaccessible to this drug.