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)].
D000624:5-Aminolevulinate Synthetase / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D015536:Down-Regulation / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects*; D005914:Globins / Q000235:genetics*; D006418:Heme / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000235:genetics / Q000378:metabolism; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D000623:Porphobilinogen Synthase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured; D015215:Zidovudine / Q000633:toxicity*
D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D006418:Heme; D015215:Zidovudine; D005914:Globins; D000624:5-Aminolevulinate Synthetase; D011163:Hydroxymethylbilane Synthase; D000623:Porphobilinogen Synthase