The initiation of cell division in a contact-inhibited mammalian cell line.

The cells of an established mouse fibroblast line, 3T3, have a high plating efficiency and grow rapidly in sparse culture, but stop growing at a very low saturation density in comparison with other lines, because 3T3 is extremely sensitive to contact inhibition of cell division. After each medium change, however, there occurs in a small fraction of the cells in a saturation density culture a series of changes that results in a single rather synchronized division 30 hours later. This is due to a macromolecular substance in the serum which appears to act by reducing the sensitivity of the cells to contact inhibition. The first recognizable event following the addition of serum to a stationary phase culture is a ten fold increase in the rate of RNA synthesis, occurring within 30 minutes. An increase in the rate of protein synthesis follows several hours later. DNA synthesis does not begin before 12 hours, but by two hours after medium change an appreciable fraction of the cells become committed to eventual DNA synthesis and cell division. The sequence of event suggests that regulation of RNA synthesis is the means by which contact inhibition controls cell division.