Growth inhibition of a human tumor cell strain by 5-fluorocytidine and 5-fluoro-2'-deoxycytidine: reversal studies.

The tumor-inhibitory and anti-leukemic activity of 5-fluorocytidine (FCR) t and 5-fluoro-2'-deoxycytidine (FCDR) has recently been reported (2, 12). Heidelberger et al. showed that 5-fluorocytosine was not active against a number of transplanted tumors in rats and mice (14, 15). In the experiments reported below the growth inhibition of H.Ep. #1 cells in culture by these 5-fluoro-substituted derivatives has been studied. Reversal of growth inhibition in the presence of selected pyrimidine derivatives was studied to provide information concerning possible mechanisms of growth inhibition. Thymidine reversed growth inhibition by FCDR in a noncompetitive manner similar to that in previously reported studies in which 5-fluoro-2'deoxyuridine (FUDR) was used as inhibitor (22). As in the case of FUDR (9), exposure of this mammalian cell strain to an appropriate concentration of FCDR for as little as 1 hour resulted in a requirement for thymidine supplement to the norreal growth medium.