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5-Fluoropyrimidine-induced DNA Damage in Human Colon Adenocarcinoma and Its Augmentation by the Nucleoside Transport Inhibitor Dipyridamole¹

Radiumhemmet, Karolinska Hospital, P. O. Box 60500 [U. L., S. L., U. N., G. W.] and Department of Histology, Karolinska Institutet [U. L., S. L.], S-104 01 Stockholm, Sweden

5-Fluorouracil and 5-fluorodeoxyuridine induce DNA lesions via two different mechanisms, one involving and the other not involving the incorporation of drug into DNA. The DNA lesions are detected by lysing cells in dilute alkali and then separating the DNA in agarose gel electrophoresis. We examine here the effect of dipyridamole, a nucleoside transport inhibitor, on the DNA lesions. We find that dipyridamole augments the levels of DNA fragmentation when the lesions are induced by the mechanism not involving the incorporation of drug. In parallel cytotoxicity is increased.

¹ This work was supported by grants from the Stockholm Cancer Society and Karolinska Institute.

² To whom requests for reprints should be addressed.

Received 7/11/88. Revised 10/13/88. Accepted 10/20/88.

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