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Food Chem Toxicol. 2016 Oct;96:107-16. doi: 10.1016/j.fct.2016.07.033. Epub 2016 Jul 29.

Endocrine activity of mycotoxins and mycotoxin mixtures.

Author information

1
CODA-CERVA, OD Chemical Safety of the Food Chain, Brussels, Belgium. Electronic address: heidi.demaegdt@coda-cerva.be.
2
CODA-CERVA, OD Chemical Safety of the Food Chain, Brussels, Belgium.
3
University of Liège, Department of Food Sciences, Liège, Belgium.
4
Université de Liège, GIGA-R, Laboratory for Organogenesis and Regeneration, Liège, Belgium.
5
CODA-CERVA, OD Chemical Safety of the Food Chain, Toxins and Natural Components, Brussels, Belgium.

Abstract

Reporter gene assays incorporating nuclear receptors (estrogen, androgen, thyroid β and PPARγ2) have been implemented to assess the endocrine activity of 13 mycotoxins and their mixtures. As expected, zearalenone and its metabolites α-zearalenol and β- zearalenol turned out to have the strongest estrogenic potency (EC50 8,7 10-10 ± 0,8; 3,1 10-11 ± 0,5 and 1,3 10-8 ± 0,3 M respectively). The metabolite of deoxynivalenol, 3-acetyl-deoxynivalenol also had estrogenic activity (EC50 3,8 10-7 ± 1,1 M). Furthermore, most of the mycotoxins (and their mixtures) showed anti-androgenic effects (15-acetyldeoxynivalenol, 3-acetyl-deoxynivalenol and α-zearalenol with potencies within one order of magnitude of that of the reference compound flutamide). In particular, deoxynivalenol and 15-acetyl-deoxynivalenol acted as antagonists for the PPARy2 receptor. When testing mixtures of mycotoxins on the same cell systems, we showed that most of the mixtures reacted as predicted by the concentration addition (CA) theory. Generally, the CA was within the 95% confidence interval of the observed ones, only minor deviations were detected. Although these reporter gene tests cannot be directly extrapolated in vivo, they can be the basis for further research. Especially the additive effects of ZEN and its metabolites are of importance and could have repercussions in vivo.

KEYWORDS:

Concentration addition; Estrogen, androgen, thyroid β and PPARγ2 reporter; Gene assays; Mixtures; Mycotoxins

PMID:
27481073
DOI:
10.1016/j.fct.2016.07.033
[Indexed for MEDLINE]

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