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NIH 3T3 cells, a mouse fibroblast cell line used as routine target cells for transfection experiments, undergo sponitaneous transformation in our experiments after they form a confluent sheet in medium containing fetal bovine serum (FBS) or lower concentration of calf serum (CS). The transformation takes the form of foci of multiplying cells among the surrounding cells which have stopped cell division. However, no focus of transformed cells could be seen in medium containing high concentration (10 %) of CS. Further experiments indicated that the frequency of transformation is highly dependent on the concentration of serum and the transformation in CS is changeable when the cells are passaged in FBS. 3H–thymidine autoradiography has been proved to be a sensitive measurement indicadtor for focus formation. Our results suggest that the high frequency of transformation and its dependence on confluency as well as on medium composition are characteristics of cell differentiation rather than mutation. The role of the NIH 3T3 cell Iine as a eaneer–initiated cell population and its accelerated transformation by ras oneogene might be considered as a form of tumor promotion is discussed.

Cell transformation as aberrant differentiation: Environmentslly dependent spontaneous transformation of NIH 3T3 cells