Gollin S M, Holmquist G P, Ledbetter D H
Am J Hum Genet. 1985 Jan;37(1):208-14.
Expression in the majority of fra(10)(q25) cases is either induced or enhanced by the presence of bromodeoxyuridine (BrdU) in the culture medium. BrdU is known to exert its effects on cells via two primary mechanisms: substitution-dependent and concentration-dependent. BrdU incorporation into DNA and BrdU concentration in the culture medium can be resolved as independent variables. The results of such experiments indicate that at three fixed levels of BrdU substitution, 100-fold variation of BrdU concentration had little or no effect on fra(10)(q25) expression. At a fixed BrdU concentration, the level of fra(10)(q25) expression rises as a function of increased BrdU substitution, approaching 100% expression at 100% substitution. Thus, BrdU induction or enhancement of fra(10)(q25) expression is clearly substitution-dependent. Iododeoxyuridine, another halogenated pyrimidine, has a similar effect. The critical time of incorporation is between 8 and 9 hrs before mitosis. After this time, removal of BrdU (and fluorodeoxyuridine [FdU]) from the culture medium followed by addition of deoxythymidine does not reverse the BrdU effect on fra(10)(q25) expression.
在大多数fra(10)(q25)病例中，培养基中溴脱氧尿苷（BrdU）的存在会诱导或增强其表达。已知BrdU通过两种主要机制对细胞发挥作用：依赖取代和依赖浓度。BrdU掺入DNA以及培养基中BrdU的浓度可作为独立变量进行解析。此类实验结果表明，在三个固定的BrdU取代水平下，BrdU浓度100倍的变化对fra(10)(q25)表达几乎没有影响。在固定的BrdU浓度下，fra(10)(q25)表达水平随着BrdU取代增加而升高，在100%取代时接近100%表达。因此，BrdU对fra(10)(q25)表达的诱导或增强显然是依赖取代的。另一种卤代嘧啶碘脱氧尿苷也有类似作用。掺入的关键时间是在有丝分裂前8至9小时之间。在此时间之后，从培养基中去除BrdU（和氟脱氧尿苷 [FdU]），然后添加脱氧胸苷，并不会逆转BrdU对fra(10)(q25)表达的影响。
