Vindeløv L L, Spang-Thomsen M, Visfeldt J, Povlsen C O, Jensen G, Nissen N I
Exp Cell Biol. 1982;50(4):216-21. doi: 10.1159/000163149.
A spontaneous change in DNA content of a human colonic carcinoma grown in nude mice was observed fortuitously. The tumor initially had a G1 cell DNA content of 1.3 times that of normal cells. Flow cytometric DNA analysis showed in transplant generation 56 the appearance of a new subpopulation which in three passages completely overgrew the original population. The DNA content of the new subpopulation was twice that of the original population. The observation supports the hypothesis of clonal evolution of tumor cell populations. The growth rates of the tumor before and after the change showed no significant difference (p greater than 0.05). Cell kinetic factors, therefore, offer no obvious explanation of how the overgrowth took place. It is not known whether the original population disappeared completely or survived as a small population below the detection limit. The heterogeneity created by clonal evolution of a tumor would be less pronounced if old subpopulations often become extinct as new ones emerge. Heterogeneity of human tumors is of clinical importance because the individual subpopulations may have different sensitivity patterns to antineoplastic drugs.
偶然观察到在裸鼠体内生长的人结肠癌DNA含量发生了自发变化。该肿瘤最初的G1期细胞DNA含量是正常细胞的1.3倍。流式细胞术DNA分析显示，在传代第56代时出现了一个新的亚群，该亚群在三代传代过程中完全取代了原始群体。新亚群的DNA含量是原始群体的两倍。这一观察结果支持肿瘤细胞群体克隆进化的假说。变化前后肿瘤的生长速率无显著差异（p大于0.05）。因此，细胞动力学因素无法明显解释这种取代是如何发生的。尚不清楚原始群体是否完全消失，还是作为一个低于检测限的小群体存活下来。如果旧的亚群在新亚群出现时经常灭绝，那么肿瘤克隆进化产生的异质性就会不那么明显。人类肿瘤的异质性具有临床重要性，因为各个亚群对抗肿瘤药物可能有不同的敏感性模式。
