Exposure of HeLa S-3 cells to 4 × 10-6 m 1-β-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 × 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-β-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.
This work was aided by grants from the National Cancer Institute (C-3811), and the Atomic Energy Commission (AT (30-1)-910).