Induction of DNA synthesis and mitosis in the absence of cellular enlargement.

Swiss 3T3 cells, starved to quiescence in low serum concentration, initiate DNA synthesis and undergo mitosis in low serum concentration (less than 0.1%) after a short exposure (2-10 min) to alkaline medium (pH 8.5-10). This study shows that initiation of DNA synthesis and mitosis can be dissociated from growth in cell size. Alkaline-stimulated cells do not increase in size before mitosis (unbalanced growth) in contrast to quiescent cells stimulated by 10% serum, which approximately double their protein content before mitosis (balanced growth). The exposure to the alkaline medium per se does not render the cells incapable of growing in size, since alkaline-treated cells, which are subsequently cultured in 10% serum, undergo balanced growth to the same extent as cells only stimulated by 10% serum without alkaline pretreatment. This study also shows that the small proportion of cells undergoing background proliferation in low serum concentration (less than 0.1%) do not increase in size before mitosis. The extent to which alkaline-stimulated cells, as well as cells undergoing background proliferation, grow in size before mitosis, is correlated to the serum concentration in the culture medium (DMEM). In 0.1% serum or less the cells do not grow in size. In 0.5% serum the cells increase in size by 30% before mitosis and complete balanced growth is achieved in medium containing 2% serum or more. These findings indicate that some macromolecular factor or factors in serum are required for growth in cell size before mitosis.