title: Unraveling the mechanisms involved in zearalenone-mediated toxicity in permanent fish cell cultures.
abstract: The world-wide occurrence of zearalenone (ZEN) as a contaminant in feed for farm animals and fish requires the evaluation of toxicity mechanisms of action of ZEN. The present study investigates possible metabolization of ZEN in fish cell lines suggesting that mainly glucuronidation takes place. It demonstrates that concentrations up to 20,000 ng ml(-1) ZEN are capable of influencing cell viability in permanent fish cell cultures in a dose-response manner with different response patterns between the five tested cell lines, whereby lysosomes appeared to be the main target of ZEN. ZEN toxicity is often discussed in the context of oxidative stress. Our study shows a biphasic response of the cell lines when reactive oxygen species (ROS) production is monitored. Damage in cells was observed by measuring lipid peroxidation, DNA strand breaks, and alterations of intracellular glutathione levels. Metabolization of ZEN, especially at concentrations above 7500 ng ml(-1) ZEN, does not prevent cytotoxicity. ZEN as an estrogenic compound may involve processes mediated by binding to estrogen receptors (ER). Since one cell line showed no detectable expression of ER, an ER-mediated pathway seems to be unlikely in these cells. This confirms a lysosomal pathway as a main target of ZEN in fish cells.
authors.affiliation: Zurich University of Applied Sciences (ZHAW), Institute of Natural Resource Sciences (IUNR), Gruental, P.O. Box, CH-8820 Waedenswil, Switzerland; Programm Man - Society - Environment, Department of Environmental Sciences, University of Basel, Vesalgasse 1, CH-4051 Basel, Switzerland. Electronic address: constanze.pietsch@zhaw.ch.
authors.forename: Constanze
authors.initials: C
authors.lastname: Pietsch
authors.affiliation: Kantonales Laboratorium Basel, Gräubernstrasse 12, CH-4410 Liestal, Switzerland.
authors.forename: Jürg
authors.initials: J
authors.lastname: Noser
authors.affiliation: Agroscope Reckenholz-Tänikon (ART), Research Station ART, Reckenholzstrasse 191, CH-8046 Zürich, Switzerland.
authors.forename: Felix E
authors.initials: FE
authors.lastname: Wettstein
authors.affiliation: Programm Man - Society - Environment, Department of Environmental Sciences, University of Basel, Vesalgasse 1, CH-4051 Basel, Switzerland; Department of Biological Sciences, University of Alberta, CW 405 Biological Sciences Building, T6G 2E9, Edmonton, AB, Canada.
authors.forename: Patricia
authors.initials: P
authors.lastname: Burkhardt-Holm
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D047628:Estrogen Receptor alpha / Q000032:analysis; D047629:Estrogen Receptor beta / Q000032:analysis; D005978:Glutathione / Q000032:analysis; D017686:Oncorhynchus mykiss; D012474:Salmon; D015025:Zearalenone / Q000633:toxicity*
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D015025:Zearalenone; D005978:Glutathione
keywords: Cytotoxicity; Estrogenic action; Genotoxicity; Mycotoxin; Oxidative stress