Rubin A L, Sneade-Koenig A, Rubin H
Virus Laboratory, University of California, Berkeley 94720.
Proc Natl Acad Sci U S A. 1992 May 1;89(9):4183-6. doi: 10.1073/pnas.89.9.4183.
NIH 3T3 cells undergo neoplastic transformation when exposed to conditions of moderate physiological growth constraint. One of several characteristics of this transformation that indicates its adaptational nature is its gradual reversibility under conditions of unconstrained growth. We explored the origins of reversibility by isolating cells from each of three highly transformed foci and comparing their focus-forming capacity with that of derivative clones and subclones. A high proportion of the parental cells made dense foci. Six of the nine clones obtained from the three foci produced foci, though the percentage varied widely. The other three clones produced no foci at all. The transformed clones were subcloned and analyzed to evaluate the possibility that the negative clones were genuine revertants, rather than being derived from a small minority of nontransformed cells surrounding or underlying the original foci. In each case the subclones varied widely in the percentage of focus-forming cells and the average was much lower than the parental clone from which they were derived. Indeed, 15 of the 53 subclonal populations produced no foci. The high degree of heterogeneity, including complete reversal of focus-forming capacity, provides additional support for the hypothesis that "spontaneous" transformation is driven by an adaptive response to moderate growth constraint rather than by one or more effectively irreversible mutations.
当暴露于适度的生理生长限制条件下时，NIH 3T3细胞会发生肿瘤转化。这种转化的几个特征之一表明其适应性本质的是，在无限制生长条件下它具有逐渐可逆性。我们通过从三个高度转化灶中的每一个分离细胞，并将它们形成灶的能力与衍生克隆和亚克隆的能力进行比较，来探索可逆性的起源。高比例的亲代细胞形成致密灶。从这三个灶获得的九个克隆中有六个产生了灶，尽管百分比差异很大。另外三个克隆根本没有产生灶。对转化克隆进行亚克隆并分析，以评估阴性克隆是真正的回复突变体的可能性，而不是来自围绕或位于原始灶周围或下方的一小部分未转化细胞。在每种情况下，亚克隆形成灶细胞的百分比差异很大，且平均值远低于它们所衍生的亲代克隆。实际上，53个亚克隆群体中有15个没有产生灶。高度的异质性，包括形成灶能力的完全逆转，为“自发”转化是由对适度生长限制的适应性反应驱动而不是由一个或多个有效不可逆突变驱动这一假设提供了额外支持。
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