Mode of action of 1-beta-D-arabinofuranosylcytosine in human lymphoblasts: differential effects of the drug on chromosomal replication.
This paper describes a novel biochemical effect of 1-beta-D-arabinofuranosylcytosine (Ara-C), a potent antitumor agent, on the process of DNA replication in cultures of human lymphoblasts (CCRF-CEM). By using short incubation periods of five minutes with 3H-thymidine and analyzing the nascent DNA by velocity sedimentation in alkaline sucrose gradients, it was found that the initial effect on DNA replication by the addition of 5 nM Ara-C is inhibition of initiation of new replicating units in DNA. A second effect of Ara-C, which is evident 30 minutes after drug addition, is a reduction in the process of elongation of these units. A model is presented to explain the mechanism by which Ara-C may cause a differential effect on DNA chain initiation and elongation in CCRF-CEM cells.
D002478:Cells, Cultured; D003561:Cytarabine / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects*; D012093:Replicon / Q000187:drug effects
D003561:Cytarabine