SPONTANEOUS TRANSFORMATION AND PROGRESSION IN CELL LINES

肿瘤中细胞的异质性似乎是肿瘤治疗的主要障碍。 成功治疗癌症。 它也是重要的理解 细胞自主生长的过程，包括转移。 的 异质性变异率的最高估计值 每10个基因中就有一个可遗传的变异5 细胞 分裂 在过去的一年里，我们能够分离出五个克隆体， Balb/3 T3细胞的后代，其刚刚经历了自发的 变换并表征其性质。 我们发现， 克隆可以通过形态学与其它克隆区分， 琼脂集落形成率（CFEag）和肿瘤形成率（ 裸鼠 这一发现的含义是，培养的细胞是如此 在转化后不稳定，基本上每个细胞都可能不同， 在一个或多个特征上与其它的不同，即，有一个真正的 根本异质性 我们还进一步研究了 这些特性在5个无性系种群中的变化 6-一个月的时间，并得出结论，类型的变化，导致 克隆体之间最初的差异也可能是 类似于肿瘤进展的持续变化。 由于这种频率 类型的变化是非常高的，涉及几个属性在一个 数量，但不协调的方式，它不太可能是由 传统的基因突变相反，它很可能是一种表观遗传 活动 这种类型的变异也可能在我们的第二大 发现，即转化细胞的某些特性被改变， 在裸鼠中肿瘤形成期间，以及当肿瘤细胞 有教养 前者与普遍接受的观点相矛盾，即细胞 通过裸鼠的传代没有改变。 我们发现我们的例子， CFEag减少超过100倍，在治疗期间经常观察到。 肿瘤形成 来自一些肿瘤的细胞恢复其原始的高CFEag 在培养物中反复传代后，但其他人没有。 即有 反应的异质性，一些变化是稳定的，另一些是不稳定的。 迄今为止的证据表明，在肿瘤发生期间， 形成和随后的培养基本上是表观遗传的， 在类型上类似于上述在转化后发生的那些。 这一结果有望为了解其起源和发展提供新的基础。 癌症的进展。 （J）

Heterogeneity of cells in tumors appears to be a major obstacle in the successful treatment of cancer. It is also of importance in understanding the progression of cells to autonomous growth including metastasis. The highest estimates of the rate of variation responsible for heterogeneity have been on the order of one heritable alteration per 105 cell divisions. In the past year we were able to isolate five clones among the progeny of a Balb/3T3 cell which had just undergone spontaneous transformation and to characterize their properties. We found that each of the clones could be distinguished from the others by morphology, colony-forming efficiency in agar (CFEag), and rate of tumor formation in nude mice. The implication of this finding is that cultured cells are so unstable soon after transformation that essentially every cell may differ from the others in one or more characteristics, i.e., that there is a truly radical heterogeneity. We have also studied the evolution of further changes in these properties among the five clonal populations over a 6-month period and conclude that the type of variation which led to the initial differences among the clones could also be responsible for continuing change akin to tumor progression. Since the frequency of this type of variation is very high and involves several properties in a quantitative but uncoordinated way, it is unlikely to be caused by conventional genetic mutations. Rather, it is likely to be an epigenetic event. This type of variation is also likely to play a role in our second major finding, which is that some properties of transformed cells are altered during tumor formation in the nude mouse and again when the tumor cells are cultured. The former contradicts the generally accepted view that cells are not changed by passage through nude mice. We find our example, that a decrease in CFEag of more than 100-fold, is frequently observed during tumor formation. Cells from some tumors regain their original high CFEag after repeated passaging in culture but others do not. That is, there is a heterogeneity of response, some changes being stable and others unstable. The evidence to date indicates the alterations in cells during tumor formation and subsequent cultivation are basically epigenetic in nature and similar in type to those described above which occur after transformation. The results promise to provide new ground for understanding the origin and progression of cancer. (J)