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Mode of action of 1-β-D-arabinofuranosylcytosine in human lymphoblasts: Differential effects of the drug on chromosomal replication

✍ Scribed by Fridland, Arnold

Publisher
John Wiley and Sons
Year
1982
Tongue
English
Weight
592 KB
Volume
10
Category
Article
ISSN
0098-1532

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✦ Synopsis

This paper describes a novel biochemical effect of 1 -P-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.

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