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)].
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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5-Aminolevulinate Synthetase / genetics
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5-Aminolevulinate Synthetase / metabolism
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Base Sequence
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Down-Regulation / drug effects
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Erythropoiesis / drug effects*
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Erythropoiesis / genetics*
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Erythropoiesis / physiology
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Gene Expression / drug effects*
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Globins / genetics*
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Heme / biosynthesis
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Heme / genetics
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Humans
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Hydroxymethylbilane Synthase / genetics
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Hydroxymethylbilane Synthase / metabolism
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Leukemia, Erythroblastic, Acute / genetics
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Leukemia, Erythroblastic, Acute / metabolism
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Molecular Sequence Data
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Oligonucleotide Probes / genetics
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Porphobilinogen Synthase / genetics
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Porphobilinogen Synthase / metabolism
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Tumor Cells, Cultured
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Zidovudine / toxicity*
Substances
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Oligonucleotide Probes
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RNA, Messenger
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Heme
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Zidovudine
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Globins
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5-Aminolevulinate Synthetase
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Hydroxymethylbilane Synthase
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Porphobilinogen Synthase