CONVERSION OF EMBRYONIC CELLS INTO TRANSFORMED CELLS

这项拨款建议的重点是，并将继续集中在一般 细胞分化机制与细胞周期的关系 肿瘤发生的机制。 细胞内控制 调节正常的定形肌细胞或软骨细胞的出现， 或色素细胞等，当发生故障时，可能会产生“肿瘤”细胞， 从60多年前Boveri时代就开始讨论。 理论 一种假设是，这些机制将正常的胚胎细胞从一个 在一个给定的谱系中，下一个隔间是那些“转化”的机制。 正常细胞转化为肿瘤细胞。 我们自己的方法集中在（1） 转化鸡肌细胞、软骨细胞和黑色素细胞， 温度敏感型劳斯肉瘤突变体，并监测代谢 这些细胞在容许和非容许温度下的反应，以及（2） 监测相同细胞类型的代谢反应， 共致癌物佛波醇-12-肉豆蔻酸酯-13-乙酸酯（PMA）。 我们发现 TS转化的成肌细胞、成软骨细胞和成黑素细胞在允许的 温度继续作为“转化细胞”复制：它们不进行终末 区分。 然而，如果这样的转化细胞被转移到非允许的 在温度下，它们最终分化成肌管，成软骨细胞， 成黑色素细胞。 同样，PMA可逆地阻止了 肌细胞、软骨细胞和黑素细胞的分化。

This grant proposal has focused, and will continue to focus, on the general problem of the relationship of the mechanisms of cell differentiation to the mechanisms of tumorigenesis. The notion that the intracellular controls regulating the emergence of a normal, definitive muscle cell, or cartilage cell, or pigment cell, etc., when malfunctioning may yield instead a "neoplastic" cell has been discussed since Boveri's time over 60 years ago. The theoretical assumption is that those mechanisms shifting normal embryonic cells from one compartment to the next in a given lineage are those mechanisms that "transform" normal cells into neoplastic cells. Our own approach has focused on (1) transforming chick myogenic, chondrogenic and melanogenic cells with a temperature-sensitive Rous sarcoma mutant, and monitoring the metabolic responses of such cells at permissive and non-permissive temperatures, and (2) monitoring the metabolic responses of the same cell types reared in the co-carcinogen, phorbol-12-myristate-13-acetate (PMA). We have found that ts-transformed myogenic, chondrogenic and melanogenic cells at permissive temperature continue to replicate as "transformed cells": they do not terminally differentiate. If however, such transformed cells are shifted to non-permissive temperature, they terminally differentiate into myotubes, chondroblasts, and melanoblasts, respectively. Similarly, PMA reversibly arrests the differentiation of myogenic, chondrogenic and melanogenic cells.