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.
D000818:Animals; D001380:Azauridine / Q000494:pharmacology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005688:Galactosamine / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental / Q000201:enzymology*; D014444:Tyrosine Transaminase / Q000096:biosynthesis*; D014500:Uracil Nucleotides / Q000502:physiology*; D014529:Uridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000502:physiology*
D014500:Uracil Nucleotides; C001943:5-fluorouridine; D005688:Galactosamine; D001380:Azauridine; D003907:Dexamethasone; D014444:Tyrosine Transaminase; D014544:Uridine Triphosphate; D014529:Uridine