ISSN:
1432-0843
Keywords:
Key Words AZT
;
S-phase cytostasis
;
cytotoxicity
;
DNA histograms
;
5-FU
;
MTX
;
flow cytometry
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract 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 μM, 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 μM, AZT produced a cytostatic rather than cytotoxic effect as indicated by viability and cell growth measurements. At 200 μM, 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00686833
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