Ardalan B, Macdonald J S, Cooney D, Schein P S
Bull Cancer. 1979;66(1):55-9.
An in vitro cell free assay system to measure phosphorylated products of 5-Fluorouracil is described. Total phosphorylated products and mono-, di and triphosphates of 5-Fluorouracil are measured along with the rate of fluorodeoxyuridylate generation. This assay has been applied to ten murine tumors and eight biopsy specimens from human breast adenocarcinomas. Phosphorylation patterns have been examined in murine tumors demonstrating in vivo sensitivity or resistance to 5-Fluorouracil. There are distinct differences in the patterns of phosphorylation between sensitive and resistant tumors. In a 5-Fluorouracil sensitive murine tumor, mono-, di and triphosphates are produced. In a resistant tumor only monosphophates are produced. Cell free supernatants from human breast tumors produce less total phosphorylation than murine tumors and some specimens produce only monophosphates whereas others produce mono-, di and triphosphates. Human tumors are in general more efficient producers of fluorodeoxyuridylate than murine tumors. These data suggest that resistance to 5-Fluorouracil may correlate with decreased concentration of di and triphosphates of 5-Fluorouracil in some murine tumors. Further experiences is required to demonstrate the value of this easily performed assay system in predicting clinical response to 5-Fluorouracil in man.
本文描述了一种用于测量5-氟尿嘧啶磷酸化产物的体外无细胞检测系统。该系统可测量5-氟尿嘧啶的总磷酸化产物以及一磷酸、二磷酸和三磷酸产物，同时还能测量氟脱氧尿苷酸的生成速率。此检测方法已应用于十种小鼠肿瘤以及八份来自人乳腺腺癌的活检标本。研究人员对在体内对5-氟尿嘧啶敏感或耐药的小鼠肿瘤的磷酸化模式进行了检测。敏感肿瘤和耐药肿瘤的磷酸化模式存在明显差异。在对5-氟尿嘧啶敏感的小鼠肿瘤中，会产生一磷酸、二磷酸和三磷酸产物。而在耐药肿瘤中，仅产生一磷酸产物。人乳腺肿瘤的无细胞上清液产生的总磷酸化产物比小鼠肿瘤少，一些标本仅产生一磷酸产物，而其他标本则产生一磷酸、二磷酸和三磷酸产物。一般来说，人肿瘤比小鼠肿瘤更有效地产生氟脱氧尿苷酸。这些数据表明，在某些小鼠肿瘤中，对5-氟尿嘧啶的耐药性可能与5-氟尿嘧啶二磷酸和三磷酸浓度降低有关。需要进一步的实验来证明这种易于操作的检测系统在预测人类对5-氟尿嘧啶临床反应方面的价值。
