Document Detail


Synergistic killing of HeLa cells by hydroxyurea and caffeine.
MedLine Citation:
PMID:  6853607     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Synchronous populations of HeLa S3 cells suffer synergistic killing during S phase in the presence of 0.5-5 mM hydroxyurea together with 5-10 mM caffeine. Both the rate and the extent of killing are greater than expected for independent action of the two drugs. Only simultaneous treatment is effective. The dependence of the synergistic killing on cell age resembles the age dependence for killing by hydroxyurea alone (greater than 3 mM), but not that by high concentrations of caffeine. In addition, rapid killing occurs if caffeine is added to cultures that have been incubated in the presence of hydroxyurea from early G1 and are blocked at the beginning of S, although such cells are killed only slowly on continued incubation in greater than or equal to 10 mM hydroxyurea alone. Furthermore, cells that are incubated with the two drugs from early G1 begin to undergo synergistic killing at about 12 h after mitotic collection, but they do not commence DNA replication for another 2-3 h if the drugs are removed. It is concluded that cells that have reached a point in the cycle identical with or close to the end of G1 are sensitive to the combination whether or not they are able to synthesize DNA, and whether or not they are sensitive to hydroxyurea alone. A tentative model is proposed: hydroxyurea is postulated to kill cells by interacting with sites of replication in DNA, and the synergism is attributed to the extra replication points that caffeine is known to induce.
Authors:
K L Beetham; P M Busse; L J Tolmach
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  115     ISSN:  0021-9541     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  1983 Jun 
Date Detail:
Created Date:  1983-07-08     Completed Date:  1983-07-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  283-90     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Caffeine / pharmacology*
Cell Survival / drug effects*
DNA Replication / drug effects
Dose-Response Relationship, Drug
Drug Synergism
Hela Cells
Humans
Hydroxyurea / pharmacology*
Interphase / drug effects
Kinetics
Grant Support
ID/Acronym/Agency:
CA 04483/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
127-07-1/Hydroxyurea; 58-08-2/Caffeine

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


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