SPONTANEOUS TRANSFORMATION AND PROGRESSION IN CELL LINES

肿瘤细胞的异质性似乎是肿瘤研究的主要障碍。 癌症的成功治疗。这对理解它也很重要 细胞自主生长的过程，包括转移。这个 对导致异质性的变异率的最高估计 大约是每105个细胞中有一个可遗传的改变 组织。在过去的一年里，我们成功地从 刚刚自发培养的Balb/3T3细胞的后代 并对它们的性质进行表征。我们发现每一个人 这些克隆人可以通过形态与其他克隆人区分开来， 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 转化后不久不稳定，基本上每个细胞都可能不同 在一个或多个特征上有别于其他人，即存在真正的 彻底的异质性。我们还研究了进一步的演变 五个克隆种群在过去一年中这些特性的变化 6个月的期间，并得出结论，导致 克隆之间的初始差异也可能是导致 类似于肿瘤进展的持续变化。因为这种情况发生的频率 类型是非常高的，并且在 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学 事件。 这种类型的变异也可能在我们的第二个专业中发挥作用 发现，转化细胞的某些属性被改变 在裸鼠体内形成肿瘤的过程中，当肿瘤细胞 有教养的。前者与普遍接受的细胞 不会因为通过裸鼠而改变。我们发现我们的例子是，一个 CFEAG下降了100倍以上，在 肿瘤的形成。一些肿瘤的细胞恢复了原来的高CFEAG 在文化中反复传代之后，其他人却没有。也就是说，有一个 反应的异质性，一些变化是稳定的，另一些变化是不稳定的。 到目前为止的证据表明在肿瘤过程中细胞的变化。 形成和随后的培养本质上是表观遗传的， 在类型上类似于上述在变形后发生的那些。 这些结果有望为理解其起源和发展提供新的依据。 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)