Arabinofuranosylcytosine-induced stimulation of thymidine kinase and deoxycytidylic deaminase activities of mammalian cultures.

DNA biosynthesis in monkey kidney and LM cell cultures. The thymidine (TdR) kinase activities of green monkey kidney (GMK or CV-1) and HeLa, but not LM or LM(TK~), cell cultures were greatly increased after ara-C treatment. A smaller increase of deoxycytidylic (dCMP) deaminase, but not of the thymidylic (TMP) kinase activity, was also found. The induction of TdR kinase activity by ara-C was prevented by cycloheximide. Addition to the cultures of arabinofuranosylthymine (ara-T), arabinofuranosyluracil (ara-U), TdR, deoxyuridine (UdR), or cytidine did not produce increases in the TdR kinase activity comparable to those produced by ara-C treatment, and the addition of TdR, UdR, or cytidine to cultures treated with ara-C did not alter the ara-C-induced stimulation of TdR kinase. Ara-T, ara-U, and ara-C did not inhibit either the enzymatic phosphorylation of UdR-3H or the deamination of dCMP-3H. Deoxycytidine, when added to cultures at the same time as ara-C, prevented the increase in TdR kinase and, when added 24 hr after the ara-C treatment, reversed the ara-C induction of TdR kinase. Mitomycin C (15-25 /ig/ml), another inhibitor of DNA biosynthesis, induced about a 4-fold increase in the TdR kinase activity. However, TdR kinase activity was not stimulated in cultures treated with 50 or 100 MK/mlmitomycin C.