Fluorouracil (Adrucil)

Fluorouracil (Adrucil) (5-FU) is an analogue of uracil with a fluorine atom at the C-5 position in place of hydrogen ^[1]. Fluorouracil is widely used in the treatment of a range of cancers, including colorectal and breast cancers, and cancers of the aerodigestive tract ^[1].

The mechanism of cytotoxicity of Fluorouracil (Adrucil) has been ascribed to the misincorporation of fluoronucleotides into RNA and DNA and to the inhibition of the nucleotide synthetic enzyme thymidylate synthase (TS) ^[1]. Fluorouracil (Adrucil) at the concentration of 770µM treated HCT116 parental cell line and its 5-FU-resistant derivatives, Fluorouracil (Adrucil) led to a G1(/S) arrest at 8 and 24 hours ^[2]. The G1 arrest was most pronounced in ContinD cells at 24 hours, whereas the S phase arrest was most pronounced in parental HCT116 cells at 24 hours ^[3].

Fluorouracil (Adrucil) beneficial effected in intestinal tumorigenesis in the Apcmin/+ mice model where a 60-80% reduction in polyps ^[4]. Fluorouracil (Adrucil) reduces body weight, exacerbates symptom severity score, increases liver weight, and decreases epididymal fat mass, and decrease in survival ^[5].

References:
[1]. Longley D B, Harkin D P, Johnston P G. 5-fluorouracil: mechanisms of action and clinical strategies[J]. Nature reviews cancer, 2003, 3(5): 330-338.
[2]. Takeda H, Haisa M, Naomoto Y, Kawashima R, Satomoto K, Yamatuji T, Tanaka N: Effect of 5-fluorouracil on cell cycle regulatory proteins in human colon cancer cell line. Jpn J Cancer Res. 1999, 90: 677-684.
[3]. De Angelis P M, Svendsrud D H, Kravik K L, et al. Cellular response to 5-fluorouracil (5-FU) in 5-FU-resistant colon cancer cell lines during treatment and recovery[J]. Molecular cancer, 2006, 5(1): 1-25.
[4]. J.M. Tucker, C. Davis, M.E. Kitchens, et al. Response to 5-fluorouracil chemotherapy is modified by dietary folic acid deficiency in Apc(Min/+) mice. Cancer Lett., 187 (2002), pp. 153-162
[5]. Sougiannis A T, VanderVeen B N, Enos R T, et al. Impact of 5 fluorouracil chemotherapy on gut inflammation, functional parameters, and gut microbiota[J]. Brain, behavior, and immunity, 2019, 80: 44-55.

氟尿嘧啶 (Adrucil) (5-FU) 是尿嘧啶的类似物，在 C-5 位置用氟原子代替氢 ^[1]。氟尿嘧啶广泛用于治疗多种癌症，包括结直肠癌、乳腺癌和呼吸消化道癌症^[1]。

氟尿嘧啶的细胞毒性作用机制（ Adrucil) 归因于氟核苷酸错误掺入 RNA 和 DNA 以及核苷酸合成酶胸苷酸合酶 (TS) ^[1] 的抑制。浓度为 770&88888181 的氟尿嘧啶 (Adrucil)；M 处理 HCT116 亲本细胞系及其 5-FU 抗性衍生物，氟尿嘧啶 (Adrucil) 在 8 小时和 24 小时导致 G1(/S) 停滞 ^{[2]< /sup>。在 24 小时时，ContinD 细胞中的 G1 期停滞最明显，而在 24 小时时亲代 HCT116 细胞中的 S 期停滞最明显[3]。}

氟尿嘧啶 (Adrucil)在 Apcmin/+ 小鼠模型中对肠道肿瘤发生产生有益影响，其中息肉减少 60-80% ^[4]。氟尿嘧啶 (Adrucil) 可减轻体重，加重症状严重程度评分，增加肝脏重量，减少附睾脂肪量，并降低生存率^[5]。