HIGH-PRESSURE LIQUID-CHROMATOGRAPHIC ANALYSIS OF 3-DEAZAURIDINE-5'-TRIPHOSPHATE IN HUMAN CANCER-CELLS

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  • 1 January 1979
    • journal article
    • research article
    • Vol. 63  (3) , 415-420
Abstract
A rapid high-pressure liquid chromatographic assay for the detection and quantitation of 3-deazauridine-5''-triphosphate (deazaUTP), the active metabolite of the anticancer drug 3-deazauridine (deazaUrd), in cell extracts is described. This procedure permits the simultaneous detection and quantitation of CTP, the cellular concentration of which is affected by treatment with deazaUrd. Human lymphoblastoid cells (line CCRF-CEM) treated with 100 nmol of deazaUrd/ml in culture accumulate deazaUTP to > 25 nmol/107 cells after 4 h. The concentration of CTP in these cells decreased exponentially with a half-life of 1.1 h. After these cells were incubated with 100 nmol of deasaUrd/ml and were resuspended in drug-free medium, the intracellular deazaUTP concentration decreased exponentially with a half-life of 3.4 h. This assay was applied to clinical studies of deazaUrd; high cellular deazaUTP concentrations were detected in human brain tumor tissue after deazaUrd infusion.

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