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Effect of Methotrexate on Incorporation and Excision of 5-Fluorouracil Residues in Human Breast Carcinoma DNA¹

Division of Medicine, Sidney Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115

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.

¹ This investigation was supported by USPHS Grants CA-28488 and CA-19589 awarded by the National Cancer Institute, Department of Health and Human Services.

² Fellow of the Medical Research Council of Canada.

³ Recipient of an American Cancer Society Jr. Faculty Research Award. To whom requests for reprints should be addressed, at the Sidney Farber Cancer Institute, 44 Binney Street, Boston, Mass. 02115.

Received 7/12/82. Accepted 9/ 9/82.

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