EFFECTS OF 3'-AZIDO-3'-DEOXYTHYMIDINE ON ERYTHROID INDUCIBLE GENE-EXPRESSION IN HUMAN K-562 LEUKEMIA-CELLS

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)].