The difference in mechanism of action of 5-fluorouracil and its nucleosides in L5178Y cells.

Publisher Website
Google Scholar
Abstract
The mechanism of antitumor activity of 5-flourouracil (FU) was studied in mouse leukemia L5178Y cells in vitro. FU increased labeled-thymidine incorporation into acid-insoluble fraction and inhibited labeled-deoxycytidine incorporation, as did 5-flourouridine (FUR) and 5-fluoro-2''-deoxyuridine (FUdR). FU and FUR inhibited labeled-uridine incorporation, FUdR did not. For reversal method at the equieffective concentration of FU, FUR or FUdR, antiproliferating effects of FU and FUR were partially reversed by thymidine and deoxyuridine, FUdR toxicity was completely abolished by both compounds. FU and FUR apparently affect thymidylate synthesis as a consequence of the conversion to deoxymononucleotide, and the site concerning functioning RNA synthesis in L5178Y cells. FUdR is a specific inhibitor of thymidylate synthesis.