The cytotoxicity of 5-fluorouracil is due to its incorporation into RNA not its inhibition of thymidylate synthase as evidenced by the use of a mouse cell mutant deficient in thymidylate synthase.

  • 1 July 1986
    • journal article
    • Vol. 77  (7) , 620-4
Abstract
The biochemical basis for the cytotoxicity of 5-fluorouracil is still controversial; it is not clear whether the mechanism involves interference with DNA metabolism or incorporation of the drug into RNA. To distinguish between these two possibilities, we took advantage of a mutant strain of the mouse mammary tumor cell line FM3A that is deficient in thymidylate synthase, which is widely believed to be the target of 5-fluorouracil. We demonstrated that the target of the cytotoxicity of 5-fluorouracil was not thymidylate synthase; instead, the cytotoxicity was positively correlated with drug incorporation into RNA under conditions where thymidine increased the incorporation of 5-fluorouracil into RNA concentration-dependently.

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