Document Detail

Inhibition of cell proliferation by interferons. 1. Effects on cell division and DNA synthesis in human lymphoblastoid (Daudi) cells.
MedLine Citation:
PMID:  6698029     Owner:  NLM     Status:  MEDLINE    
Treatment of Daudi cells with human lymphoblastoid interferons for up to 5 days progressively inhibits cell proliferation. For the first 3 days cells continue to grow but with prolonged doubling times; subsequently, net proliferation ceases and is accompanied by a loss of cell viability. We have investigated the changes in labelling of DNA with radioactive precursors which occur during the first phase of the response to interferon treatment. We have shown previously [Gewert et al. (1981) Eur. J. Biochem. 116, 487-492] that inhibition of incorporation of [3H]thymidine into DNA can be accounted for by impairment of thymidine transport and thymidine kinase activity. In spite of this inhibition, the total intracellular dTTP pool is larger in interferon-treated than in control cells. Because of these changes it has been necessary to use other methods to determine whether interferon treatment inhibits the overall rate of DNA synthesis. The results of experiments employing (a) moderately high thymidine concentrations or (b) incorporation of radioactivity from deoxynucleoside triphosphates into DNA in detergent-lysed or permeabilised cell systems indicate that there is in fact relatively little inhibition of the overall rate of DNA synthesis in cells exposed to up to 100 units/ml of interferons for at least 48 h. Furthermore, a similar proportion of cells incorporate [3H]thymidine in control and interferon-treated cultures and there is only a small decrease in the number of cells in S phase after interferon treatment, as revealed by fluorescence-activated cell sorting. These results indicate that cell proliferation may be regulated in this system by a mechanism in which there is a loss of coordination between the initiation of DNA synthesis and the subsequent events required for cell division.
D R Gewert; G Moore; V J Tilleray; M J Clemens
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of biochemistry / FEBS     Volume:  139     ISSN:  0014-2956     ISO Abbreviation:  Eur. J. Biochem.     Publication Date:  1984 Mar 
Date Detail:
Created Date:  1984-04-25     Completed Date:  1984-04-25     Revised Date:  2007-07-23    
Medline Journal Info:
Nlm Unique ID:  0107600     Medline TA:  Eur J Biochem     Country:  GERMANY, WEST    
Other Details:
Languages:  eng     Pagination:  619-25     Citation Subset:  IM    
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MeSH Terms
Biological Transport / drug effects
Cell Division / drug effects*
Cell Membrane Permeability
Cells, Cultured
DNA / biosynthesis
Interferon Type I / pharmacology*
Lymphocytes / cytology,  drug effects
Thymidine / metabolism
Reg. No./Substance:
0/Interferon Type I; 50-89-5/Thymidine; 9007-49-2/DNA

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

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