Document Detail


Specific effect of 5-fluorouracil on alpha-fetoprotein gene expression during the in vitro mouse embryonic stem cell differentiation.
MedLine Citation:
PMID:  20448262     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Embryonic stem (ES) cells are considered an important alternative to develop in vitro screening methods for embryotoxicity. Mouse ES cells can be cultured as cell suspension aggregates termed "embryoid bodies" (EBs) in which cells start to differentiate. We have studied the expression of several genes in the presence of a wide range of concentrations of 5-fluorouracil (5-FU). This well-established embryotoxic compound completely inhibited cell viability at 200 nmol/L in monolayer cultures. At lower concentrations, 5-FU led to decrease in the expression of the alpha-fetoprotein gene, a marker of the visceral endoderm, in the EBs. However, the expression of several mesodermal gene markers was not significantly affected at these concentrations. These results suggest a high sensitivity of the visceral endoderm differentiation to 5-FU. Therefore, the quantification of the alpha-fetoprotein gene after exposure to potential embryotoxicants should be considered an additional end point in future embryotoxicity assays in vitro with ES cells.
Authors:
David Pamies; Néstor Vicente-Salar; Miguel A Sogorb; Enrique Roche; Juan A Reig
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of toxicology     Volume:  29     ISSN:  1092-874X     ISO Abbreviation:  Int. J. Toxicol.     Publication Date:    2010 May-Jun
Date Detail:
Created Date:  2010-05-07     Completed Date:  2010-08-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9708436     Medline TA:  Int J Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  297-304     Citation Subset:  IM    
Affiliation:
Instituto de Bioingenieria, Universidad Miguel Hernández de Elche, Elche, Spain.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, Differentiation / genetics,  metabolism
Cell Differentiation / drug effects*
Cell Line
Cell Survival / drug effects
Dose-Response Relationship, Drug
Embryonic Stem Cells / cytology,  drug effects*,  metabolism
Endoderm / cytology,  drug effects,  metabolism
Endpoint Determination
Fluorouracil / toxicity*
Gene Expression Regulation, Developmental / drug effects*
Membrane Proteins / genetics,  metabolism
Mesoderm / cytology,  drug effects,  metabolism
Mice
Myosin Heavy Chains / genetics,  metabolism
Teratogens / toxicity*
Time Factors
Toxicity Tests / methods
Vascular Endothelial Growth Factor Receptor-2 / genetics,  metabolism
alpha-Fetoproteins / genetics,  metabolism*
beta Catenin / genetics,  metabolism
Chemical
Reg. No./Substance:
0/Amn protein, mouse; 0/Antigens, Differentiation; 0/Catnb protein, mouse; 0/Membrane Proteins; 0/Myosin Heavy Chains; 0/Teratogens; 0/alpha-Fetoproteins; 0/beta Catenin; 0/beta myosin heavy chain protein, mouse; 51-21-8/Fluorouracil; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-2

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


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