Document Detail


Hydroxyurea-induced cell death as related to cell cycle in mouse and human T-lymphoma cells.
MedLine Citation:
PMID:  3499975     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The association between DNA precursor synthesis, cell cycle perturbations, and cell death caused by the anticancer drug hydroxyurea was investigated in mouse and human T-lymphoma cells. Hydroxyurea inhibits the enzyme ribonucleotide reductase, leading to decreased deoxyribo nucleoside triphosphate pools and an accumulation of cells in early S-phase of the cell cycle. We wished to clarify the mechanism of cell death caused by hydroxyurea in concentrations that can be obtained therapeutically. At a 60-microM concentration of the drug, giving 25% growth inhibition during 24 h, no increase in the number of dead cells was observed as determined by cell flow calculations and density gradient centrifugation. However, the removal of hydroxyurea led to 10-30% cell loss during the following 12-h period. In parallel, there was an increase in DNA precursor levels and a rapid progression of cells through S- and G2 phases of the cell cycle. The isolated dead cells showed no overrepresentation of any cell cycle phase. The results demonstrate that, although the toxic effects of low concentrations of hydroxyurea are minimal, the drug-induced unbalanced growth state can cause substantial cell death during a posttreatment period.
Authors:
S Skog; B Tribukait; B Wallström; S Eriksson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer research     Volume:  47     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1987 Dec 
Date Detail:
Created Date:  1988-01-21     Completed Date:  1988-01-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  6490-3     Citation Subset:  IM    
Affiliation:
Department of Medical Radiobiology, Karolinska Institut, Stockholm, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Cycle / drug effects*
Cell Survival / drug effects
Deoxyribonucleosides / metabolism
Humans
Hydroxyurea / pharmacology*
Lymphoma / pathology*
Mice
T-Lymphocytes
Tumor Cells, Cultured / drug effects
Chemical
Reg. No./Substance:
0/Deoxyribonucleosides; 127-07-1/Hydroxyurea

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


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