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Genotoxicity of a freshwater cyanotoxin, cylindrospermopsin, in two human cell lines: Caco‐2 and HepaRG
Author(s) -
Bazin Emmanuelle,
Mourot Annick,
Humpage Andrew R.,
Fessard Valérie
Publication year - 2010
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.20539
Subject(s) - cylindrospermopsin , genotoxicity , micronucleus test , biology , cyanotoxin , micronucleus , microbiology and biotechnology , pharmacology , toxicity , chemistry , genetics , microcystin , cyanobacteria , organic chemistry , bacteria
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. Environ. Mol. Mutagen. 2010. © 2009 Wiley‐Liss, Inc.

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