McMillan T J, Stephens T C, Steel G G
Br J Cancer. 1986 Jun;53(6):753-9. doi: 10.1038/bjc.1986.129.
The sensitivity to melphalan of clones derived from individual lung colonies produced by i.v. injection of cells of the MT murine mammary carcinoma (caMT) and its melphalan-resistant sub-line (MTME16) has been examined. A degree of clonal heterogeneity was observed which was greater than could be explained by experimental variation. The distribution of melphalan sensitivities in both wild-type caMT and MTME16 raises questions as to the validity of a two-compartment model of drug-resistance development in tumours. A more complex model, possibly involving a continuous spectrum of drug sensitivity, is required. Differences in the sensitivity of the clonal lines of wild-type caMT in various passages were observed and this would appear to be due to phenotypic instability in these lines. This suggests that to use survival data from clones which have been passaged many times for predicting the response of the parent tumour may be misleading.
通过静脉注射MT小鼠乳腺癌（caMT）细胞及其美法仑耐药亚系（MTME16）所产生的单个肺集落衍生克隆对美法仑的敏感性已被检测。观察到一定程度的克隆异质性，其程度大于实验变异所能解释的范围。野生型caMT和MTME16中美法仑敏感性的分布对肿瘤耐药性发展的双室模型的有效性提出了质疑。需要一个更复杂的模型，可能涉及药物敏感性的连续谱。观察到野生型caMT不同传代的克隆系敏感性存在差异，这似乎是由于这些系中的表型不稳定性所致。这表明，使用多次传代克隆的存活数据来预测亲本肿瘤的反应可能会产生误导。
