Genotoxic potential associated with low levels of the Fusarium mycotoxins nivalenol and fusarenon X in a human intestinal cell line.
This study aims to assess the genotoxic potential of nivalenol (NIV) and fusarenon X (FusX), produced by various Fusarium on cereals. Toxins were applied in time and dose-dependent experiments to the human enterocyte-like Caco-2 cell-line, both in dividing (undifferentiated) and in 10-12 days post-confluent cells (differentiated). Genotoxicity was evaluated through the alkaline Comet assay in a concentration range defined for each toxin as below the cytotoxicity threshold IC(10), determined by the MTS and the neutral red assays, to prevent false positive results because of DNA damage stemming from necrosis. Thus, genotoxicity was explored in the sub-cytotoxic 0-0.5 microM and 0-0.05 microM ranges respectively for NIV and FusX as the latter was found about 10-fold more cytotoxic than NIV. For both toxins, a 3h exposure did not cause any DNA damage, unlike after 24 and 72 h exposure in post confluent Caco-2 cells where DNA damage was significantly observed with a dose-dependent relationship. In dividing cells, only FusX increases DNA strand breaks in the 0.01-0.05 microM range after 72 h. These results demonstrated the existence of a genotoxic potential for NIV and FusX at low exposure levels and could contribute to the risk assessment process of these toxins that are of growing concern.
Bony
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S
UMR INRA-DGER Mycotoxines et Toxicologie Comparée des Xénobiotiques, Ecole Nationale Vétérinaire de Lyon, 1, av. Bourgelat, F-69280 Marcy l'Etoile, France. s.bony@vet-lyon.fr
Olivier-Loiseau
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L
Carcelen
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M
Devaux
A
A
D018938:Caco-2 Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005670:Fusarium / Q000737:chemistry*; D006801:Humans; D009153:Mutagens / Q000633:toxicity*; D009183:Mycotoxins / Q000633:toxicity*; D009499:Neutral Red / Q000378:metabolism; D013778:Tetrazolium Salts / Q000378:metabolism; D013997:Time Factors; D014255:Trichothecenes / Q000633:toxicity*
D009153:Mutagens; D009183:Mycotoxins; D013778:Tetrazolium Salts; D014255:Trichothecenes; C002469:fusarenon-X; D009499:Neutral Red; C038405:nivalenol