Kinetics of Effect of 1-β-D-Arabinofuranosylcytosine, Its 5′-Palmitoyl Ester, 1-β-D-Arabinofuranosyluracil, and Tritiated Thymidine on the Viability of Cultured Leukemia L1210 Cells

Rates of reduction in viability of replicating cultured L1210 cell populations exposed to 1-β-D-arabinofuranosylcytosine [ara-C (3.2–3,000 μg/ml)] were relatively independent of concentrations used. At lower concentrations (0.32–1.0 μg/ml) a finite interval was observed during which cell killing was...

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Bibliographic Details
Published in:JNCI : Journal of the National Cancer Institute 1972-03, Vol.48 (3), p.685-695
Main Authors: Wilkoff, Lee J., Dulmadge, Elizabeth A., Lloyd, Harris H.
Format: Article
Language:English
Subjects:
Animals
Arabinose - pharmacology
Cell Survival - drug effects
Cells, Cultured
Depression, Chemical
Esters - pharmacology
Half-Life
In Vitro Techniques
Kinetics
Leukemia L1210 - prevention & control
Mice
Nitrosourea Compounds - pharmacology
Nucleosides - pharmacology
Osmolar Concentration
Palmitic Acids
Thymidine - pharmacology
Tritium
Uracil - pharmacology
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Summary:Rates of reduction in viability of replicating cultured L1210 cell populations exposed to 1-β-D-arabinofuranosylcytosine [ara-C (3.2–3,000 μg/ml)] were relatively independent of concentrations used. At lower concentrations (0.32–1.0 μg/ml) a finite interval was observed during which cell killing was not detected; this interval occurred before reduction of viability in the cell populations. At concentrations between 0.032 and 0.32 μg/ml, this agent could produce significant reductions in viability of cell populations provided the exposure was of sufficient duration. Cultured L1210 cells maintained under nonproliferative conditions were not sensitive to this agent or to hydroxyurea, but were sensitive to 1,3-bis(2-chloroethyl)-1-nitrosourea. The kinetics of cell killing when proliferating cultured L1210 cells were exposed to high specific-activity tritiated thymidine were essentially like those observed with ara-C at concentrations >10 μg/ml. The 5′-palmitoyl ester of ara-C reduced the viability of cell populations exposed to effective concentrations of this agent. The kinetics of cell killing depended on the concentration of the ester. 1-β-D-Arabinofuranosyluracil, the deamination product of ara-C, was relatively nontoxic for proliferating cultured L1210 cells.
ISSN:0027-8874
1460-2105
DOI:10.1093/jnci/48.3.685