REGULATION OF TYROSINE AMINOTRANSFERASE ACTIVITY IN TWO LIVER-DERIVED PERMANENT CELL LINES

The regulation of tyrosine aminotransferase (TAT) activity has been examined in two liver-derived heteroploid cell lines. One (hepatoma tissue culture cells [HTC]) was derived from a hepatoma, the other (rat liver culture cells [RLC]) was derived from normal liver. The two cell lines show the following striking similarities in the control of this specific protein: (a) The kinetics of TAT induction by dexamethasone phosphate (DxP) are similar in randomly growing cells of both lines; (b) During mitosis and early G₁ phase of the cell cycle TAT activity cannot be induced by DxP in either cell line; (c) 2–3 h into G₁, when both lines become sensitive to inducer, basal enzyme activity declines to a new steady-state level; (d) Preinduced cells collected in mitosis show approximately twice the level of TAT activity as fully induced, randomly growing cultures and this activity is maintained in early G₁ with or without the inducer; and (e) Inhibition of RNA synthesis by 5 µg/ml of actinomycin D in preinduced, synchronized cells allows TAT activity to remain at constitutive levels throughout G₁, even in the absence of inducer. These results are presented in support of a previously described model which states that glucocorticoid hormones exert posttranscriptional control of the synthesis of specific proteins in mammalian cells.