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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1995-4-13
pubmed:abstractText
The mechanism of synergy between 3'-azido-3'-deoxythymidine (AZT) and anticancer agents was investigated with emphasis on cell-cycle events. Exposure of exponentially growing WiDr human colon carcinoma cells to AZT resulted in synchronization of cells in the S phase of the cell cycle. Following treatment with AZT at 50 or 200 microM, 62% +/- 3% or 82% +/- 4% of the cells were in the S phase as compared with 36% +/- 2% in the control. Bromodeoxyuridine uptake studies revealed that the synchronized cells actively synthesized DNA. At concentrations of up to 200 microM, AZT produced a cytostatic rather than cytotoxic effect as indicated by viability and cell growth measurements. At 200 microM, AZT-induced synchronization was significant (P = < 0.001) after 12 h of drug exposure, reached a maximum at 24 h, and reversed to baseline levels by 72 h even in the continued presence of the drug. This indicates that AZT-induced cytostasis is a transient and reversible effect. The cell-cycle events seen with AZT in WiDr cells were also observed in eight of nine human tumor cell lines tested. Isobologram analysis of WiDr cells preexposed to AZT for 24 h and then exposed to either AZT-5-fluorouracil or AZT-methotrexate for a further 72 h revealed synergy between AZT and the anticancer agents, indicating that AZT-induced synchronization may have therapeutic benefits.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0344-5704
pubmed:author
pubmed:issnType
Print
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
489-95
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:7882457-Antineoplastic Agents, pubmed-meshheading:7882457-Breast Neoplasms, pubmed-meshheading:7882457-Carcinoma, pubmed-meshheading:7882457-Cell Division, pubmed-meshheading:7882457-Cell Survival, pubmed-meshheading:7882457-Colonic Neoplasms, pubmed-meshheading:7882457-Computer Simulation, pubmed-meshheading:7882457-DNA, Neoplasm, pubmed-meshheading:7882457-Drug Synergism, pubmed-meshheading:7882457-Flow Cytometry, pubmed-meshheading:7882457-Fluorouracil, pubmed-meshheading:7882457-Humans, pubmed-meshheading:7882457-Leukemia, pubmed-meshheading:7882457-Melanoma, pubmed-meshheading:7882457-Methotrexate, pubmed-meshheading:7882457-Pancreatic Neoplasms, pubmed-meshheading:7882457-S Phase, pubmed-meshheading:7882457-Tumor Cells, Cultured, pubmed-meshheading:7882457-Zidovudine
pubmed:year
1995
pubmed:articleTitle
Synchronization of cells in the S phase of the cell cycle by 3'-azido-3'-deoxythymidine: implications for cell cytotoxicity.
pubmed:affiliation
Division of Cell Biology, Wellcome Research Laboratories, Research Triangle Park, NC 27709.
pubmed:publicationType
Journal Article, Comparative Study