Dexamethasone Phosphate-induced Synthesis of Tyrosine Aminotransferase in Hepatoma Tissue Culture Cells STUDIES Ok’ THE EARLY PHASES OF INDUCTION AND OF THE STEROID REQUIREMENT FOR MAIN- TENANCE OF THE INDUCED RATE OF SYNTHESIS

The studies reported herein further define the induction of tyrosine aminotransferase in hepatoma tissue culture cells, a tissue culture line developed from a rat hepatoma. These studies show that: 1. Tyrosine aminotransferase induction is due to an increase in the rate of synthesis, as shown by specific immunochemical precipitation of the enzyme labeled in vivo, contiming earlier findings. 2. There are no detectable nonantigenic precursors of tyrosine aminotransferase; hence synthesis seems to be from free amino acids. 3. Removal of the glucocorticoid from fully induced cells results in a prompt fall in tyrosine aminotransferase activity and a decline in its rate of synthesis. This decrease in activity is accompanied by a loss of antigenic activity of tyrosine aminotransferase, indicating that the enzyme is converted or degraded to a nonantigenic form. 4. After addition of inducer, a lag period of about 2 hours is observed before tyrosine aminotransferase activity begins to increase. In several experiments, the rate of synthesis was seen to increase more rapidly than the rise in catalytic activity, but only after a 60to 90-min lag. “Enzyme-forming potential” is enhanced within 30 min after addition of the inducer and is the earliest effect of glucocorticoid hormones yet detected in this induction system.