Effect of methotrexate on incorporation and excision of 5-fluorouracil residues in human breast carcinoma DNA.

We have demonstrated recently that 5-fluorouracil (FUra) residues incorporate in eukaryotic DNA. In the present study, we extend these findings and monitor the effect of methotrexate on the formation of FUra DNA. The results demonstrate that methotrexate treatment has little effect on the incorporation of FUra or 5-fluorodeoxyuridine in DNA obtained from MCF-7 human breast carcinoma cells. More importantly, we demonstrate that FUra residues are excised from MCF-7 DNA and that methotrexate enhances the excision process. This excision of FUra from eukaryotic DNA may contribute to the cytotoxicity and mutagenicity of these fluorinated pyrimidines.