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5-Hexyl-2'-deoxyuridine Blocks the Cytotoxic Effects of 5-Fluorodeoxyuridine or Deoxyadenosine in Leukemia L1210 Cells in Culture¹

Department of Internal Medicine, University of South Florida College of Medicine, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612 [J. G. C., M. C. H.], and First Institute of Pathology and Experimental Cancer Research, Semmelweis Medical University, Budapest, Hungary [A. J., K. L.]

Antitumor agents which block the de novo synthesis of nucleotides can be circumvented by the presence of salvage pathways for the reutilization of nucleobases and nucleosides. Studies have been carried out which show that 5-hexyl-2'-deoxyuridine (HdUrd) effectively blocks the cytotoxic effects of deoxyadenosine and fluorodeoxyuridine in L1210 cells. Although HdUrd (500 µM) had essentially no effect on the growth of L1210 cells in culture, the total uptake of [¹⁴C]cytidine into these cells was inhibited 99% by this concentration of HdUrd. The inhibitory effects of fluorodeoxyuridine (FdUrd) and deoxyadenosine could be completely prevented by the presence of HdUrd (200 µM). The growth inhibitory effects of fluorouracil were not prevented by HdUrd. Dipyridamole prevented the inhibition of L1210 cell growth by FdUrd but not by deoxyadenosine or fluorouracil. 5-Isopropyl-, 5-pentyl-, and 5-octyldeoxyuridine were not effective in preventing the cytotoxic effects of deoxyadenosine. The data suggest that HdUrd might be useful in blocking the salvage of nucleosides, thereby potentiating the effects of inhibitors of de novo nucleotide synthesis.

¹ Supported by Grant CA 27398 from the National Cancer Institute, USPHS. This work was initiated as part of the United States-Hungarian Cancer Research Agreement.

² To whom requests for reprints should be addressed, at Department of Internal Medicine, University of South Florida, Box 19, 12901 Bruce B. Downs Boulevard, Tampa, FL 33612-4799.

Received 12/ 5/89. Revised 3/27/90.