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Effects of 3'-azido-3'-deoxythymidine on erythroid inducible gene expression in human K-562 leukemia cells
D A Fowler1, D A Weidner, J P Sommadossi
1Department of Pharmacology and Toxicology, University of Alabama at Birmingham, USA.
Abstract:
We previously demonstrated that 3'-azido-3'-deoxythymidine (AZT) down regulates hemoglobin (Hb) synthesis and globin gene expression. That inhibition may therefore result either from a direct effect on globin gene transcription or an indirect effect through inhibition of K-562 cell induction, thereby leading to inhibition of other inducible genes of heme biosynthesis. The present results demonstrate that inhibition of globin gene expression by AZT is a direct gene effect rather than a general inhibition of K-562 cell induction as demonstrated by the absence of AZT effects on expression of three other erythroid inducible genes [erythroid-specific aminolevulate synthase (ALAS-E), aminolevulinic acid dehydrogenase (ALAD), and erythroid-specific porphobilinogen deaminase (PBGD-E)].