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  • Title: Inhibition of deoxyribonucleic acid chain initiation: a new mode of action for 1-beta-D-arabinofuranosylcytosine in human lymphoblasts.
    Author: Fridland A.
    Journal: Biochemistry; 1977 Nov 29; 16(24):5308-12. PubMed ID: 921933.
    Abstract:
    A novel biochemical effect of 1-beta-D-arabinofuranosylcytosine (ara-C) on DNA replication in cultured human lymphoblasts is described. By incubating the cells with [3H] thymidine for 5 min and analyzing the nascent DNA by velocity sedimentation in alkaline sucrose gradients, it was possible to discern the initial effect of a very low concentration of drug (5 nM) on DNA replication. During the first 30 min of incubation, ara-C inhibited the initiation of new replicating units of DNA but did not affect the elongation of previously initiated units. A later effect was the reduction of the rate of DNA chain elongation. A model, based on the incorporation of ara-C into nascent DNA, is presented to account for a differential effect of the drug on DNA chain initiation and elongation in mammalian cells.
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