Wilson G D
Gray Laboratory, Mount Vernon Hospital, Northwood, England.
Acta Oncol. 1991;30(8):903-10. doi: 10.3109/02841869109088242.
The study of human tumour proliferation has been facilitated by the development of monoclonal antibodies recognizing halogenated pyrimidines. Flow cytometry can be used to detect the incorporation of bromodeoxyuridine (BUdR) into DNA simultaneously with the measurement of total DNA content. We have studied in excess of 600 tumours using in vivo administration of BUdR. The cell kinetic information generated from this approach is more complete than can be obtained from in vitro incubation with DNA precursors such as tritiated thymidine (3HTdR) or by single parameter DNA analysis. The duration of S-phase (Ts) can be estimated in addition to the labelling index (LI). From these two parameters, the potential doubling time (Tpot) can be calculated. Our data show a wide variation in Ts as well as LI, making both these parameters important variants in determining overall proliferation. Although there is tremendous variation in Tpot between tumours of the same and different types, the median values are surprisingly short at around 5 days. A close relationship exists between the presence of DNA aneuploidy and the proliferation parameters. The clinical relevance of Tpot is currently being assessed independently in two trials of accelerated versus conventional fractionation.
识别卤代嘧啶的单克隆抗体的发展推动了对人类肿瘤增殖的研究。流式细胞术可用于检测溴脱氧尿苷（BUdR）掺入DNA的情况，同时测量总DNA含量。我们通过体内给予BUdR研究了600多个肿瘤。这种方法产生的细胞动力学信息比用氚标记的胸腺嘧啶核苷（3HTdR）等DNA前体进行体外孵育或通过单参数DNA分析所获得的信息更完整。除标记指数（LI）外，还可估计S期持续时间（Ts）。根据这两个参数，可以计算潜在倍增时间（Tpot）。我们的数据显示Ts和LI存在很大差异，这使得这两个参数成为决定总体增殖的重要变量。尽管同一类型和不同类型肿瘤之间的Tpot差异巨大，但中位数出奇地短，约为5天。DNA非整倍体的存在与增殖参数之间存在密切关系。目前正在两项加速分割与传统分割的试验中分别评估Tpot的临床相关性。
