Sklower S L, Jenkins E C, Anderson M L, Chan C B, Brown W T
Am J Med Genet. 1986 Jan-Feb;23(1-2):483-90. doi: 10.1002/ajmg.1320230140.
Induction of some fragile sites including fragile X [fra(X)] depends on the depletion of thymidine monophosphate (TMP) from the culture medium. This can be accomplished by use of inhibitors such as 5-fluorodeoxyuridine (FUdR) and by culturing cells in medium deficient in folate and TMP. FUdR inhibits the activity of thymidylate synthase (TS), thereby depleting cells of TMP. To determine the degree of FUdR inhibition of TS under routine cytogenetic culture conditions, we modified the tritiated dUMP TS method for use in short-term whole blood cultures stimulated with phytohemagglutinin. TS inhibition was highly variable across whole blood cultures from 30 individuals exposed to FUdR during the last 24 hours of a 4 day culture. If an additional dose of FUdR was added 12 hours before harvest, TS inhibition usually increased. These findings have a potential impact on the use of FUdR for the diagnosis of the fra(X) syndrome.
包括脆性X [fra(X)]在内的一些脆性位点的诱导取决于培养基中胸苷单磷酸（TMP）的耗尽。这可以通过使用5-氟脱氧尿苷（FUdR）等抑制剂以及在缺乏叶酸和TMP的培养基中培养细胞来实现。FUdR抑制胸苷酸合成酶（TS）的活性，从而使细胞中的TMP耗尽。为了确定在常规细胞遗传学培养条件下FUdR对TS的抑制程度，我们对氚标记的dUMP TS方法进行了改进，用于用植物血凝素刺激的短期全血培养。在4天培养的最后24小时内暴露于FUdR的30名个体的全血培养中，TS抑制差异很大。如果在收获前12小时添加额外剂量的FUdR，TS抑制通常会增加。这些发现对使用FUdR诊断fra(X)综合征有潜在影响。
