Establishment of mouse embryo cells in vitro: Relationship of DNA synthesis, senescence and malignant transformation

Mouse embryo cells exhibited a decline in proliferative capacity with increasing in vitro age. The ability of these monolayer cells to undergo DNA synthesis as a function of culture age was examined, and a progressive decline in the percentage of cells able to incorporate [ 3H]thymidine was found; in this respect they resembled normal human cells in culture. Instead of phasing out after a period of time, however, the mouse cultures were taken over by a continuously proliferating population of cells which displayed an elevated growth rate with a correspondingly large fraction of cells which incorporated [ 3H]thymidine. At a time subsequent to this in vitro alteration, after the cultures had stabilized as a permanent cell line, the cells developed the capability of forming tumors when tested in vivo. These results suggest that the acquisition of indeterminate lifespan and a high growth rate in culture may be early events in a multi-step process leading to malignancy.