title: Endocrine activity of mycotoxins and mycotoxin mixtures.
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.
authors.affiliation: CODA-CERVA, OD Chemical Safety of the Food Chain, Brussels, Belgium. Electronic address: heidi.demaegdt@coda-cerva.be.
authors.forename: Heidi
authors.initials: H
authors.lastname: Demaegdt
authors.affiliation: CODA-CERVA, OD Chemical Safety of the Food Chain, Brussels, Belgium.
authors.forename: Britt
authors.initials: B
authors.lastname: Daminet
authors.affiliation: CODA-CERVA, OD Chemical Safety of the Food Chain, Brussels, Belgium.
authors.forename: Annick
authors.initials: A
authors.lastname: Evrard
authors.affiliation: University of Liège, Department of Food Sciences, Liège, Belgium.
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Scippo
authors.affiliation: Université de Liège, GIGA-R, Laboratory for Organogenesis and Regeneration, Liège, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Muller
authors.affiliation: CODA-CERVA, OD Chemical Safety of the Food Chain, Brussels, Belgium.
authors.forename: Luc
authors.initials: L
authors.lastname: Pussemier
authors.affiliation: CODA-CERVA, OD Chemical Safety of the Food Chain, Toxins and Natural Components, Brussels, Belgium.
authors.forename: Alfons
authors.initials: A
authors.lastname: Callebaut
authors.affiliation: CODA-CERVA, OD Chemical Safety of the Food Chain, Brussels, Belgium.
authors.forename: Karine
authors.initials: K
authors.lastname: Vandermeiren
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D052244:Endocrine Disruptors / Q000737:chemistry / Q000633:toxicity*; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D009183:Mycotoxins / Q000737:chemistry / Q000633:toxicity*; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D011042:Poisons / Q000737:chemistry / Q000633:toxicity*; D011944:Receptors, Androgen / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism
chemical_list: D052244:Endocrine Disruptors; D009183:Mycotoxins; D047495:PPAR gamma; D011042:Poisons; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011988:Receptors, Thyroid Hormone; D008156:Luciferases
keywords: Concentration addition; Estrogen, androgen, thyroid β and PPARγ2 reporter; Gene assays; Mixtures; Mycotoxins