Roos G, Stenram U
Department of Pathology, University of Lund, University Hospital, Sweden.
J Surg Oncol. 1997 Jul;65(3):155-8. doi: 10.1002/(sici)1096-9098(199707)65:3<155::aid-jso2>3.0.co;2-5.
5-fluorouracil (5-FU) exerts its effects mainly by its incorporation into RNA and inhibition of DNA synthesis. Its toxicity may therefore be estimated by measuring its incorporation into RNA. Protein malnutrition has been considered to increase the toxicity of 5-FU.
Rats with a hepatoma implanted into the liver were fed on either a 25% or a 0% casein diet for 1 week. On the last day, they were infused via the hepatic artery with a therapeutic dose of 3H-5-FU. Its incorporation into RNA was measured in hepatoma and several normal tissues.
Protein deprivation increased the incorporation of 5-FU into liver and intestinal RNA. Incorporation into hepatoma RNA did not increase significantly, but the ratio, liver/hepatoma RNA incorporation, remained unchanged.
Protein deprivation might increase the toxicity of 5-FU on liver and intestine.
5-氟尿嘧啶(5-FU)主要通过掺入RNA和抑制DNA合成发挥作用。因此,可通过测量其掺入RNA的情况来评估其毒性。蛋白质营养不良被认为会增加5-FU的毒性。
将肝癌植入肝脏的大鼠分别喂食含25%或0%酪蛋白的饮食1周。在最后一天,经肝动脉给它们输注治疗剂量的3H-5-FU。测量其在肝癌组织和几种正常组织中掺入RNA的情况。
蛋白质缺乏增加了5-FU在肝脏和肠道RNA中的掺入量。在肝癌RNA中的掺入量没有显著增加,但肝脏/肝癌RNA掺入率保持不变。
蛋白质缺乏可能会增加5-FU对肝脏和肠道的毒性。