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 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.