Document Detail


Tetrahydrouridine, cytidine analogues, and hemoglobin F.
MedLine Citation:
PMID:  2579548     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
5-Azacytidine (azaC) has previously been shown to raise Hb F levels in the repeatedly phlebotomized baboon (PCV: around 20%). The administration of tetrahydrouridine (THU), an inhibitor of the enzymatic conversion of azaC to 5-azauridine, made it possible to reduce the amount of azaC and also of 2-deoxy-5-azacytidine (d-azaC) by more than 90% and still achieve maximal Hb F elevations. However, the granulocytopenia, usually occurring after 5-azaC, was not altered by the lowering of the dosages in the presence of THU. Thus, the granulocytopenia is not due to 5-azauridine or other catabolic products resulting from deamination. It is also unlikely that it is caused by a direct influence of azaC on RNA since d-azaC also causes granulocytopenia. The persistence of reticulocytosis throughout the treatment with azaC or d-azaC makes it appear likely that the observed increase in Hb F levels to more than 60% of total hemoglobin is not due to a cytotoxic effect on erythropoiesis resulting in a shift of cell populations toward greater immaturity, but to a direct influence of the drug on the regulation of gamma globin chain production.
Authors:
J DeSimone; P Heller; R E Molokie; L Hall; D Zwiers
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of hematology     Volume:  18     ISSN:  0361-8609     ISO Abbreviation:  Am. J. Hematol.     Publication Date:  1985 Mar 
Date Detail:
Created Date:  1985-04-04     Completed Date:  1985-04-04     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  7610369     Medline TA:  Am J Hematol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  283-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Agranulocytosis / etiology
Animals
Azacitidine / analogs & derivatives,  pharmacology*,  toxicity
Cytidine Deaminase / antagonists & inhibitors
Fetal Hemoglobin / biosynthesis*,  genetics
Gene Expression Regulation / drug effects
Globins / genetics
Granulocytes / enzymology
Papio
Tetrahydrouridine / pharmacology*
Uridine / analogs & derivatives*
Grant Support
ID/Acronym/Agency:
HL 20920-06/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
18771-50-1/Tetrahydrouridine; 320-67-2/Azacitidine; 58-96-8/Uridine; 776B62CQ27/decitabine; 9004-22-2/Globins; 9034-63-3/Fetal Hemoglobin; EC 3.5.4.5/Cytidine Deaminase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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