重组人干扰素α-2a（rIFN-α-2a；500或5,000 IU/mL）或[6RS] 亚叶酸（[6RS]LV；1微摩尔/升）均能增强5-氟尿嘧啶（FUra）对两种人类结肠腺癌细胞系（GC3/c1；VRC5/c1）的细胞毒性活性，增幅为2.6至3.2倍，在72小时内曝露。当三种药物合并使用时，FUra的细胞毒性增强了3.2至4.3倍（总增强10至14倍）。在临床可达到的rIFN-α-2a和[6RS]LV浓度下，可增强FUra的细胞毒性。dThd（20微摩尔/升）可以逆转作用，尽管喹唑啉类特异性嘧啶酸合成酶抑制剂CB3717的活性未被rIFN-α-2a增强。数据表明，在胸腺嘧啶酸合成酶或DNA水平，5-氟嘧啶核苷对生化调节和相互作用的需求。

Recombinant human interferon-alpha 2a (rIFN-alpha 2a; 500 or 5,000 IU/mL) or [6RS] leucovorin ([6RS]LV; 1 microM) each potentiated the cytotoxic activity of 5-fluorouracil (FUra) by 2.6- to 3.2-fold during 72 hr exposures in two human colon adenocarcinoma cell lines (GC3/c1; VRC5/c1). When all three agents were combined, FUra cytotoxicity was further potentiated by 3.2- to 4.3-fold (total 10- to 14-fold). Potentiation of FUra cytotoxicity occurred at clinically achieveable concentrations of rIFN-alpha 2a and [6RS]LV. Effects were reversed by dThd (20 microM), although the activity of CB3717, a quinazoline-based, specific inhibitor of thymidylate synthase, was not potentiated by rIFN-alpha 2a. Data suggest the requirement of a 5-fluoropyrimidine for biochemical modulation and interaction at the level of thymidylate synthase or DNA.