Mode of action of 5-fluorouridine 5'-phosphate in vivo and in vitro.

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Abstract
5-Fluorouridine and 1-.beta.-D-arabinofuranosylcytosine are active against various tumors as antimetabolites. Antitumor activity and the mode of action of their nucleotides, 5-fluorouridine 5''-phosphate and 1-.beta.-D-arabinofuranosylcytosine 5''-phosphate, were examined. 5-Fluorouridine 5''-phosphate was active similar to the nucleoside against [mouse] L1210 leukemia, but the nucleotide showed higher therapeutic ratio than 5-fluorouracil and 5-fluorouridine. The mode of action of these nucleotides was examined by the incorporation of labeled precursors into acid-insoluble fraction of the cells for 30 min. Inhibition patterns of these nucleotides were the same as those of the nucleosides, but the potency of the nucleotides was very weak, and increased with time. Analysis showed that these nucleotides were dephosphorylated on the cell surface and the dephosphorylation was greater than that of phenolphthalein monophosphate. 5-Fluorouridine 5''-phosphate was considered to be a good candidate for an antitumor agent.

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