Yoshida M, Hoshi A, Kuretani K
J Pharmacobiodyn. 1980 Aug;3(8):374-9. doi: 10.1248/bpb1978.3.374.
The mechanism of antitumor activity of 5-fluorouracil (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-fluorouridine (FUR) and 5-fluoro-2'-deoxyuridine (FUdR). FU and FUR inhibited labeled-uridine incorporation but 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 though FUdR toxicity was completely abolished by both compounds. These results demonstrate that FU and FUR affect not only thymidylate synthesis as a consequence of the conversion to deoxymononucleotide, but also the site concerning functioning RNA synthesis in L5178Y cells, and the FUdR is a specific inhibitor of thymidylate synthesis.
在体外对小鼠白血病L5178Y细胞研究了5-氟尿嘧啶（FU）的抗肿瘤活性机制。FU增加了标记胸腺嘧啶核苷掺入酸不溶性部分，并抑制了标记脱氧胞苷的掺入，5-氟尿苷（FUR）和5-氟-2'-脱氧尿苷（FUdR）也有同样的作用。FU和FUR抑制了标记尿苷的掺入，但FUdR没有。对于FU、FUR或FUdR等效应浓度下的逆转方法，FU和FUR的抗增殖作用部分被胸腺嘧啶核苷和脱氧尿苷逆转，尽管两种化合物都完全消除了FUdR的毒性。这些结果表明，FU和FUR不仅由于转化为脱氧单核苷酸而影响胸苷酸合成，而且还影响L5178Y细胞中与功能性RNA合成有关的位点，并且FUdR是胸苷酸合成的特异性抑制剂。
