Increased uptake of 5-fluorouracil by Ehrlich ascites tumor cells with some additives and metabolite analysis.
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.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects; D003857:Deoxyuridine / Q000494:pharmacology; D003902:Detergents / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D005472:Fluorouracil / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011073:Polyamines / Q000494:pharmacology; D012334:RNA, Neoplasm / Q000378:metabolism; D012267:Ribosemonophosphates / Q000494:pharmacology; D014529:Uridine / Q000494:pharmacology
D003902:Detergents; D011073:Polyamines; D012334:RNA, Neoplasm; D012267:Ribosemonophosphates; C031154:ribose 1-phosphate; C031302:2-deoxyribose 1-phosphate; D000255:Adenosine Triphosphate; D004492:Edetic Acid; D005472:Fluorouracil; D003857:Deoxyuridine; D014529:Uridine