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

Abstract

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.

• Authors: E M Giesen, G Beck, A Holstege, D O Keppler
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 655 Issue 1 Pg. 34-40 (Aug 27 1981) ISSN: 0006-3002 [Print] Netherlands
• PMID: 6167286 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Uracil Nucleotides
• 5-fluorouridine
• Galactosamine
• Azauridine
• Dexamethasone
• Tyrosine Transaminase
• Uridine Triphosphate
• Uridine

Topics

• Animals
• Azauridine (pharmacology)
• Cells, Cultured
• Dexamethasone (pharmacology)
• Enzyme Induction (drug effects)
• Galactosamine (pharmacology)
• Liver Neoplasms, Experimental (enzymology)
• Tyrosine Transaminase (biosynthesis)
• Uracil Nucleotides (physiology)
• Uridine (analogs & derivatives, pharmacology)
• Uridine Triphosphate (physiology)