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Action of 1-ß-D-Arabinofuranosyl-5-fluorocytosine on the Nucleic Acid Metabolism and Viability of HeLa Cells¹

Divisions of Biophysics and Biological Chemistry, Sloan-Kettering Institute for Cancer Research, New York, New York

Exposure of HeLa S-3 cells to 4 x 10^-6 M 1-ß-D-arabinofuranosyl-5-fluorocytosine (ara-FC)² arrested cell division. In the 1st 24-hr period, RNA and protein increased by a factor of about 2 while there was only a slight increase in the amount of DNA. The cell viability (defined as the capacity of a cell to grow out into a macroscopic clone) declined sharply following exposure to 1 x 10^-6 M ara-FC for more than 1 generation time. These results strongly suggest a state of unbalanced growth similar to that previously observed with 5-fluorodeoxyuridine, excess thymidine and 1-ß-D-arabinofuranosylcytosine (ara-C). The inhibition by ara-FC could be effectively prevented by simultaneous exposure of cells to a 100-fold excess of deoxycytidine, but not cytidine, thymidine, or deoxyuridine.

These results, strikingly similar to those previously obtained with are-C, demonstrate that replacement of a hydrogen atom at the 5-position of the cytosine moiety of ara-C by the considerably more electronegative fluorine atom does not appreciably alter several important biochemical sites of inhibitory activity.

¹ This work was aided by grants from the National Cancer Institute (C-3811), and the Atomic Energy Commission (AT (30-1)-910).

Received 1/17/66.