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Studies on the Growth Inhibition and Metabolism of 2'-Deoxy-2'-fluorocytidine in Cultured Human Lymphoblasts¹

McEachern Laboratory and Department of Biochemistry, University of Alberta, Edmonton, Alberta, T6G 2E1, Canada [L. W. B., G. A. L.], and Department of Biology, University of California, San Diego, California 92037 [S. S. H., D. H. S.]

The nucleoside 2'-deoxy-2'-fluorocytidine (FCdR) inhibits the growth of various human lymphoblastic cell lines in culture. FCdR is deaminated to 2'-deoxy-2'-fluorouridine and phosphorylated to the triphosphate level. Two additional FCdR-containing metabolites, comprising about 50% of the acid-soluble metabolites, were also detected. The FCdR incorporated into acid-insoluble material was primarily in DNA. Deoxycytidine protected these cell lines from growth inhibition by FCdR, but for only a limited time.

¹ This work was supported by grants from the National Cancer Institute of Canada, by NIH Grant CA 12960, and by the University of California (Cancer Research Funds). Part of this work was done while Dr. S. S. Hendler and Dr. D. H. Shanahoff were at the Salk Institute, San Diego, Calif. 92112. An initial report was presented at the 162nd National Meeting, American Chemical Society, September 12 to 17, 1971.

² To whom reprint requests should be addressed.

Received 1/ 8/74. Accepted 4/10/74.

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