Abstract
Treatment of bone marrow progenitor cells (BMPC) with zidovudine (AZT) at various concentrations (0.5 to 20 microM) in vitro for 24 hr caused a concentration-dependent decrease in erythropoietin (Epo) receptor expression. The decrease in Epo receptors correlated with a decline in mRNA levels of the receptor. These results suggest that AZT-induced down-regulation of Epo receptor expression followed by loss of Epo-receptor mediated signal transduction is a significant contributory factor to AZT-induced erythroid toxicity.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Differentiation / drug effects
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Colony-Forming Units Assay
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Didanosine / pharmacology
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Dose-Response Relationship, Drug
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Down-Regulation
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Hematopoietic Stem Cells / drug effects*
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Hematopoietic Stem Cells / metabolism
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Male
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Mice
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RNA, Messenger / metabolism
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Receptors, Erythropoietin / antagonists & inhibitors
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Receptors, Erythropoietin / drug effects*
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Receptors, Erythropoietin / metabolism
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Signal Transduction / drug effects
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Zidovudine / pharmacology*
Substances
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RNA, Messenger
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Receptors, Erythropoietin
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Zidovudine
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Didanosine