Mechanism of Growth Inhibition by 5-Fluorouracil. Reversal Studies with Pyrimidine Metabolites in Vitro

Summary Continuous exposure to FU at a concentration of 0.05 μg/ml was uniformly toxic for a tissue culture strain of Ehrlich ascites tumor, ELD. Of the normal pyrimidine metabolites tested in the presence of FU, neither U, UR, or OA exerted a protective effect against FU toxicity. However, TdR did...

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Veröffentlicht in:Experimental biology and medicine (Maywood, N.J.) N.J.), 1969-07, Vol.131 (3), p.1068-1072
Hauptverfasser: Reeves, William J., Cailleau, Relda
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container_title Experimental biology and medicine (Maywood, N.J.)
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creator Reeves, William J.
Cailleau, Relda
description Summary Continuous exposure to FU at a concentration of 0.05 μg/ml was uniformly toxic for a tissue culture strain of Ehrlich ascites tumor, ELD. Of the normal pyrimidine metabolites tested in the presence of FU, neither U, UR, or OA exerted a protective effect against FU toxicity. However, TdR did have a protective effect at a concentration of 5 μg/ml, permitting normal growth of ELD cells. At higher FU concentrations, TdR had less protective action. Brief (1-3 hr) exposures to FU at high concentrations (5-50 μg ml) produced toxicity which could be counteracted when the FU exposure was followed by cell washing and continuous exposure to TdR. These findings suggest that TdRP formation is the step most sensitive to FU.
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subjects Animals
Carcinoma, Ehrlich Tumor - metabolism
Culture Techniques
Depression, Chemical
DNA, Neoplasm - biosynthesis
Fluorouracil - toxicity
Mice
Nucleotides - biosynthesis
Orotic Acid - pharmacology
RNA, Neoplasm - biosynthesis
Thymidine - pharmacology
Uridine - pharmacology
title Mechanism of Growth Inhibition by 5-Fluorouracil. Reversal Studies with Pyrimidine Metabolites in Vitro
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