Cell cycle arrest as a basis of enhancement of 1-β- d-arabinofuranosylcytosine anabolism in human lymphoblastoid RPMI 6410 cells cultured with 3-deazauridine

Abstract

The antiproliferative effect of 1-β- D-arabinofuranosylcytosine (araC) on RPMI 6410 cells in culture was potentiated in the presence of 3-deazauridine (DU). When the culture medium contained DU, proliferation ceased and cells did not progress in the replication cycle beyond early S phase. When cells from such DU-treated cultures were transferred to DU-free medium containing Cyd, a rapid, partially synchronous resumption of DNA synthesis occurred. Under these circumstances, the activity of dCyd kinase, assessed using araC as substrate, was enhanced in unfractionated extracts of DU-treated cells relative to extracts of untreated cells. It is suggested that the presence of DU in culture medium stopped the progression of cells through the replication cycle, arresting them in an araC-sensitive portion of S phase, and that the enhanced ability of DU-treated cells to anabolize dCyd and araC derived, at least in part, from the accumulation of cells in S phase, a portion of the cell cycle in which dCyd kinase is elevated.