Exposure of murine leukemia L1210 cells to graded doses of 5-fluorouracil for 24 hr led to a progressive increase in cell surface hydrophobicity, inhibition of cell division, and an increased cell volume. Among the effects associated with fluorouracil treatment were inhibition of thymidylate synthetase, decreased incorporation of leucine into glycoprotein, and an apparently increased incorporation of thymidine into DNA and of glucosamine into glycoprotein. The latter effects are believed to be caused by depleted metabolite pools. Short-term treatment of L1210 cells with the drug altered only levels of thymidylate synthetase. Cell surface changes therefore appear to be related to long-term effects of fluorouracil associated with impaired synthesis of membrane glycoprotein.

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Research supported by Grant CA 23243 from the National Cancer Institute, Department of Health, Education, and Welfare, and by a grant from the Ulrick & Bay Foundation of New York.

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