Open AccessMode of action of 1‐β‐D‐arabinofuranosylcytosine in human lymphoblasts: Differential effects of the drug on chromosomal replication
Author(s) -
Fridland Arnold
Publication year - 1982
Publication title -
medical and pediatric oncology
Language(s) - English
Resource type - Journals
eISSN - 1096-911X
pISSN - 0098-1532
DOI - 10.1002/mpo.2950100709
Subject(s) - lymphoblast , medicine , mode of action , replication (statistics) , drug , drug action , mechanism of action , action (physics) , cancer research , virology , pharmacology , genetics , biology , cell culture , in vitro , toxicology , physics , quantum mechanics
This paper describes a novel biochemical effect of 1 ‐β‐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 3 H‐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.