Document Detail


Genotoxicity of a freshwater cyanotoxin, cylindrospermopsin, in two human cell lines: Caco-2 and HepaRG.
MedLine Citation:
PMID:  19902517     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cylindrospermopsin (CYN), a cyanotoxin produced by certain freshwater cyanobacteria, causes human intoxications and animal mortalities. CYN is a potent inhibitor of protein- and glutathione-synthesis. Preliminary evidence for in vivo tumor initiation has been found in mice but the mechanism remains unclear. Several in vitro and in vivo studies demonstrate that CYN is genotoxic and requires metabolic activation. In the present study, the genotoxicity of CYN was assessed in human hepatocyte and enterocyte cell lines, which are models for CYN target organs. The cytokinesis-block micronucleus assay was conducted on liver-derived HepaRG cells and colon-derived Caco-2 cells. Each cell-type was exposed to CYN in both the differentiated and the undifferentiated states, and both with and without the cytochrome P450 inhibitor, ketoconazole, to determine the involvement of metabolism in CYN genotoxicity. CYN increased the frequency of micronuclei in binucleated cells (MNBNC) in both Caco-2 and HepaRG cells. Moreover, ketoconazole reduced both the genotoxicity and cytotoxicity caused by CYN. Our results confirm the involvement of metabolic activation of CYN in mediating its toxicity and suggest that CYN is progenotoxic.
Authors:
Emmanuelle Bazin; Annick Mourot; Andrew R Humpage; Val?rie Fessard
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Environmental and molecular mutagenesis     Volume:  51     ISSN:  1098-2280     ISO Abbreviation:  Environ. Mol. Mutagen.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-15     Completed Date:  2010-04-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8800109     Medline TA:  Environ Mol Mutagen     Country:  United States    
Other Details:
Languages:  eng     Pagination:  251-9     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Wiley-Liss, Inc.
Affiliation:
Agence Fran?aise de S?curit? Sanitaire des Aliments, Unit? de Toxicologie G?n?tique des Contaminants Alimentaires, Foug?res, France.
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MeSH Terms
Descriptor/Qualifier:
Caco-2 Cells
Cell Line
Humans
Ketoconazole / pharmacology
Micronucleus Tests
Mutagens / toxicity*
Uracil / analogs & derivatives*,  metabolism,  toxicity
Chemical
Reg. No./Substance:
0/Mutagens; 143545-90-8/cylindrospermopsin; 65277-42-1/Ketoconazole; 66-22-8/Uracil

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


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