Abstract
These studies concern the question whether diffusible repressors control the syntheses of enzymes in mammalian cells. First, clonal sublines of baby hamster kidney (BHK 21/13) cells in culture were selected in stepwise fashion for resistance to aminopterin. These sublines survived in concentrations of aminopterin that were up to 10(4) times higher than those tolerated by wild-type cells because they contained up to 125 times as much folate reductase, probably due to overproduction of the enzyme. When five resistant sublines were hybridized to wild-type lines, 32 of 35 hybrid clones contained intermediate levels of reductase activity. This suggests that overproduction of reductase is not due to loss of a diffusible repressor.