2-deoxyribose-1-phosphate--(alpha-d-erythro)-isomer and Carcinoma--Ehrlich-Tumor

Both ribose 1-phosphate and deoxyribose 1-phosphate, which were effective in increasing the formation of antineoplastic fluoronucleotides and fluoro-RNA from 5-fluorouracil (5-FU) in the intact cells of Ehrlich mouse ascites tumor, potentiated the antitumor effect of 5-FU. Ethylenediaminetetraacetate, which stimulates the formation of only fluororibonucleotides from 5-FU in intact Ehrlich tumor cells, was ineffective in the potentiation of 5-FU antitumor activity. The relationship between the increased metabolite formation from 5-FU and the antitumor effect of 5-FU is discussed.

Topics: Animals; Carcinoma, Ehrlich Tumor; Cells, Cultured; Drug Therapy, Combination; Edetic Acid; Fluorouracil; Leukemia L1210; Mice; Pentosephosphates; Ribosemonophosphates

We studied the uptake of radioactive 5-fluorouracil (FUra) by the intact cells of Ehrlich ascites tumor in the presence of various coreactants with FUra such as uridine (Urd), deoxyuridine (dUrd), ribose 1-phosphate (Rib1P), and deoxyribose 1-phosphate (dRib1P). Radioactivity uptake by the cells was increased when FUra-6-14C was incubated with Rib1P or dRib1P, while the uptake was not stimulated with Urd or dUrd. The increased formation of antineoplastic ribo- and deoxyribo-nucleotides of FUra in the acid-soluble fraction was also observed in the same incubation with Rib1P or dRib1P. Also, some detergents, ethylenediaminetetraacetic acid (EDTA), adenosine 5'-triphosphate (ATP), and polyamines were examined. EDTA stimulated the uptake of radioactivity from the FUra by the cells. However, the other compounds exhibited no effect on the uptake of FUra alone or FUra plus dRib1P, except of ATP showing somewhat increase of radioactivity uptake. The above results suggest that the coadministration of FUra together with Rib1P or/and dRib1P, which are stimulants for the formation of FUra-deoxynucleotides from FUra, may be able to potentiate the chemotherapeutic effect of FUra.

Topics: Adenosine Triphosphate; Animals; Carcinoma, Ehrlich Tumor; Cell Membrane Permeability; Deoxyuridine; Detergents; Edetic Acid; Fluorouracil; Male; Mice; Mice, Inbred Strains; Polyamines; Ribosemonophosphates; RNA, Neoplasm; Uridine

In order to acquire a biochemical fundamental knowledge on the enhancement of antitumor effect with 5-fluorouracil or its masked derivatives, this investigation was undertaken to determine the amounts of antineoplastic metabolic precursors formed from 5-fluorouracil-6-14C in the presence of various substrates by crude enzyme extracts from Ehrlich mouse ascites tumor cells and normal mouse liver. Combinations of uridine plus ribose 1-phosphate and deoxyuridine plus deoxyribose 1-phosphate were effective for the enhancement of 5-fluorouridine and 5-fluorodeoxyuridine formation, respectively. 5-Fluorouridine and 5-fluorodeoxyuridine are respectively utilizable for the syntheses of the antineoplastic compounds, 5-fluorouridine 5'-triphosphate and 5-fluoro-2'-deoxyuridine 5'-monophosphate. These results suggest that the coadministration of the above substrates together with 5-fluorouracil would be advantageous in the enhancement of the antitumor effect of 5-fluorouracil or its masked derivatives.

Topics: Animals; Ascites; Carcinoma, Ehrlich Tumor; Deoxyuridine; Fluorouracil; In Vitro Techniques; Liver; Male; Mice; Ribosemonophosphates; Uridine

In expectation of the elevated formation of an antineoplastic metabolite from 5-fluorouracil (5FU), we examined the additive effect of 2-deoxy-alpha-D-ribose 1-phosphate (dRib1P) and/or 2'-deoxyuridine (dUrd) upon the formation of 5-fluoro-2'-deoxyuridine (5FdUrd) or proximately more antineoplastic 5-fluoro-2'-deoxyuridine 5'-monophosphate (5FdUMP) from 5FU using a crude extract and the whole cells of Ehrlich tumor cells. The amounts of 5FdUrd formed from 5FU by a crude extract were increased in the presence of dRib1P and dUrd, although it was stimulated much more by dRib1P than by dUrd. In the intact cells, the conversion of 5FU to 5FdUMP was also increased by dRib1P, while the presence both of dRib1P and dUrd enhanced the formation of 5FdUrd rather than that of 5FdUMP. These results suggest that the coadministration of 5FU with dRib1P may increase the chemotherapeutic effect of 5FU.

Topics: Animals; Carcinoma, Ehrlich Tumor; Deoxyuracil Nucleotides; Deoxyuridine; Fluorodeoxyuridylate; Fluorouracil; Kinetics; Mice; Pentosephosphates; Ribosemonophosphates