title: Cytotoxicity and Hsp 70 induction in Hep G2 cells in response to zearalenone and cytoprotection by sub-lethal heat shock.
abstract: Zearalenone (ZEN) is a mycotoxin with several adverse effects in laboratory and domestic animals. The mechanism of ZEN toxicity that involves mainly binding to oestrogen receptors and inhibition of macromolecules synthesis is not fully understood. Using human hepatocytes Hep G2 cells as a model, the aim of this work was (i) to investigate the ability of ZEN to induce heat shock proteins Hsp 70 and (ii) to find out the mechanisms of ZEN cytotoxicity by examining cell proliferation and protein synthesis. Our study demonstrated that ZEN induces Hsp 70 expression in a time and dose-dependant manner; this induction occurs at non-cytotoxic concentrations, it could be therefore considered as a biomarker of toxicity. A cytoprotective effect of Hsp 70 was elicited when Hep G2 cells were exposed to Sub-Lethal heat shock prior to ZEN treatment and evidenced by a reduced ZEN cytolethality. This cytoprotection suggests that Hsp 70 may constitute an important cellular defence mechanism. Finally, our data show that ZEN is cytotoxic in Hep G2 cells by inhibiting cell proliferation and total protein synthesis and pointed out oxidative damage as possible pathway involved in ZEN toxicity; however, other investigations are needed to further confirm Zen induced oxidative stress.
authors.affiliation: Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Rue Avicenne, 5019 Monastir, Tunisia.
authors.forename: Wafa
authors.initials: W
authors.lastname: Hassen
authors.forename: Emna
authors.initials: E
authors.lastname: El Golli
authors.forename: Isabelle
authors.initials: I
authors.lastname: Baudrimont
authors.forename: A Théophile
authors.initials: AT
authors.lastname: Mobio
authors.forename: M Moncef
authors.initials: MM
authors.lastname: Ladjimi
authors.forename: E Edmond
authors.initials: EE
authors.lastname: Creppy
authors.forename: Hassen
authors.initials: H
authors.lastname: Bacha
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D018869:Heat-Shock Response; D006801:Humans; D020128:Inhibitory Concentration 50; D014176:Protein Biosynthesis / Q000187:drug effects; D015025:Zearalenone / Q000633:toxicity*
chemical_list: D004968:Estrogens, Non-Steroidal; D018840:HSP70 Heat-Shock Proteins; D015025:Zearalenone