Rubin H, Arnstein P, Chu B M
Cancer Res. 1984 Nov;44(11):5242-8.
During repeated passage of BALB/3T3 cells and testing for anchorage-independent growth, a single transformed clone was isolated from agar, and five subclones were derived from it. These subclones differed from one another in morphology on a solid substratum, efficiency and size of colony formation in agar, and rate of tumor formation in nude mice. With weekly passage over a period of 6 months, the differences in morphology and growth in agar gradually decreased. The subclone which produced the fastest-growing tumors in nude mice after 4 weeks of culture produced the slowest-growing tumors after 18 weeks, and a change in the opposite direction was made by another subclone. There was no difference among the subclones in growth rate on plastic. The distribution of chromosome numbers was heterogeneous but overlapping in all the primary subclones at 16 and 24 weeks, with no statistically significant difference in the mean number of chromosomes per subclone. An extremely high degree of variation must have occurred to produce the multiple differences between the subclones, and the same type of variation could have been responsible for the subsequent changes with repeated passage. The high frequency and graded nature of the changes and the concurrent involvement of several traits suggest an epigenetic basis for the variation.
在对BALB/3T3细胞进行多次传代并检测其非贴壁依赖性生长的过程中，从琼脂中分离出一个转化克隆，并由此衍生出五个亚克隆。这些亚克隆在固体基质上的形态、在琼脂中的集落形成效率和大小以及在裸鼠中的肿瘤形成速率彼此不同。经过6个月每周一次的传代，形态和在琼脂中的生长差异逐渐减小。在培养4周后在裸鼠中产生生长最快肿瘤的亚克隆，在18周后产生生长最慢的肿瘤，而另一个亚克隆则发生了相反方向的变化。亚克隆在塑料上的生长速率没有差异。在16周和24周时，所有初代亚克隆的染色体数目分布都是异质但重叠的，每个亚克隆的平均染色体数目没有统计学上的显著差异。为了产生亚克隆之间的多重差异，必然发生了极高程度的变异，并且相同类型的变异可能是随后传代过程中变化的原因。这些变化的高频率和分级性质以及多个性状的同时涉及表明这种变异具有表观遗传基础。
