Document Detail


Schedule-dependent enhancement of 1-beta-D-arabinofuranosylcytosine incorporation into HL-60 DNA by deoxyguanosine.
MedLine Citation:
PMID:  6584206     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We studied the ability of the purine deoxynucleoside deoxyguanosine (dGuo) to enhance 1-beta-D-arabinofuranosylcytosine (ara-C) incorporation into DNA of HL-60 cultured human leukemia cells. The effects of dGuo on ara-C incorporation into DNA were compared to those of thymidine (dThd), a pyrimidine deoxynucleoside known to augment ara-C effects both in vitro and in vivo. Both deoxynucleosides doubled the cells in the S phase of the cell cycle within the exposure periods (up to 48 hr) and concentrations (10 to 1000 microM) tested. Both deoxynucleosides enhanced ara-C incorporation into DNA equally. However, dThd and dGuo differed in the schedule required to achieve this effect. Simultaneous exposure of cells to ara-C and dThd increased ara-C incorporation into DNA approximately 3.5-fold. Preincubation of cells with dThd for 16 hr prior to the addition of ara-C further enhanced ara-C incorporation into DNA (to approximately 5-fold) in direct proportion to the dThd-induced increase in cells in S phase. Preincubation was essential for dGuo, since 16-hr preincubation of cells with concentrations as low as 30 microM caused augmentation of ara-C incorporation into DNA; but simultaneous exposure of cells to dGuo and ara-C caused no augmentation of ara-C incorporation into DNA. The augmentation of ara-C incorporation into DNA caused by preincubation of the cells with dGuo results from a number of factors, including the cytokinetic effect of increasing the percentage of cells in S phase and the reduction of intracellular dCTP pools. Maximal dGuo enhancement of ara-C incorporation into DNA (approximately 5-fold) required greater than 100 microM dGuo, 16-hr preincubation with dGuo, and final incubation of cells with ara-C after removal of dGuo. We explain this further augmentation of ara-C incorporation into DNA caused by the removal of dGuo prior to adding ara-C by our observed inhibition of ara-C phosphorylation by dGuo concentrations greater than 100 microM.
Authors:
D D Ross; S A Akman; C C Joneckis; E Yang; N R Bachur
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer research     Volume:  44     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1984 Apr 
Date Detail:
Created Date:  1984-05-04     Completed Date:  1984-05-04     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1530-5     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Cell Line
Clone Cells
Cytarabine / metabolism*,  toxicity
DNA Replication / drug effects
Deoxyguanosine / pharmacology*
Flow Cytometry
Humans
Kinetics
Leukemia, Lymphoid / metabolism
Phosphorylation
Thymidine / metabolism,  pharmacology
Tritium / diagnostic use
Chemical
Reg. No./Substance:
10028-17-8/Tritium; 147-94-4/Cytarabine; 50-89-5/Thymidine; 961-07-9/Deoxyguanosine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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