Inhibition of tyrosine aminotransferase induction by UTP deficiency and its reversal by 5-fluorouridine in cultured hepatoma cells

Hepatoma tissue culture cells, grown in the presence of d-galactosamine and 6-azauridine, demonstrate a strong reduction of the intracellular UTP pool that can be replenished by formation of UTP from uridine and FUTP from 5-fluorouridine within 2 h. Concomitantly with the UTP deficiency, a decrease of dexamethasone-induced tyrosine aminotransferase activity occurs. 5-Fluorouridine, as compared to uridine, is even more efficient in restoring the activity of tyrosine aminotransferase. Treatment of the cells with d-galactosamine alone results in a minor lowering of UTP that is not followed by the inhibition of the enzyme induction. However, the administration of d-galactosamine, simultaneously or at any time up to 5 h before or after dexamethasone, leads to a 1.5- to 2-fold higher induction (superinduction) which appears 24 h later.