title: Comparative study of cytotoxicity and oxidative stress induced by deoxynivalenol, zearalenone or fumonisin B1 in human intestinal cell line Caco-2.
abstract: Fusarium species infestations of cereals crops occur worldwide. Fusarium toxins such as, deoxynivalenol (DON), zearalenone (ZEN) and fumonisin B1 (FB1) have been shown to cause diverse toxic effects in animals and also suspected of disease causation in humans. From the literature and mechanistic point of view, DON binds to the ribosomal peptidyl-transferase and inhibits protein synthesis specifically and DNA synthesis consequently. ZEN known to be genotoxic, binds to 17-beta-estradiol receptors, induces lipid peroxidation, cell death and inhibits protein and DNA synthesis. FB1 disrupts sphingolipid metabolism, induces lipid peroxidation altering the cell membrane and causing cell death. We intended to compare DON, ZEN and FB1 (1-150 microM) cytotoxic effect and the pathways leading to cell death and related to oxidative stress and macromolecules syntheses in a human intestinal cell line in order to tentatively classify them according to their respective potential toxicity. The comparison reveals that all three mycotoxins bear, at variable degree, the capability of inducing lipid peroxidation (MDA production) and could be classified above 10 microM in decreasing potency order FB1>DON>ZEN. This effect seems to be related to their common target that is the mitochondria as revealed by MTT test and seemingly not related to sphingoids accumulation concerning FB1. DON and ZEN also adversely affect lysosomes in contrast to FB1. The three mycotoxins inhibit protein synthesis with respective IC50 of 5, 8.8 and 19 microM for DON, FB1 and ZEN confirming that protein synthesis is a specific target of DON. DNA synthesis is inhibited by DON, ZEN and FB1 with respective IC50 of 1.7, 10 and 20 microM. However at higher concentrations DNA synthesis seems to be restored for FB1 and DON suggesting a promoter activity. Altogether the potency of the three mycotoxins in macromolecules inhibition is DON>ZEN>FB1 in Caco-2 cells. It appears then that FB1 acts rather through lipid peroxidation while DON affects rather DNA and protein synthesis.
authors: Toxicology Department, University of Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux, France.
authors: James H
authors: JH
authors: Kouadio
authors: Théophile A
authors: TA
authors: Mobio
authors: Isabelle
authors: I
authors: Baudrimont
authors: Serge
authors: S
authors: Moukha
authors: Sébastien D
authors: SD
authors: Dano
authors: E Edmond
authors: EE
authors: Creppy
mesh_terms: D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004396:Coloring Agents / Q000737:chemistry; D004261:DNA Replication / Q000187:drug effects / Q000502:physiology; D005562:Formazans / Q000737:chemistry; D037341:Fumonisins / Q000633:toxicity*; D006801:Humans; D020128:Inhibitory Concentration 50; D008315:Malondialdehyde / Q000378:metabolism; D009499:Neutral Red / Q000737:chemistry; D018384:Oxidative Stress / Q000187:drug effects*; D013778:Tetrazolium Salts / Q000737:chemistry; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014255:Trichothecenes / Q000633:toxicity*; D015025:Zearalenone / Q000633:toxicity*
chemical_list: D004396:Coloring Agents; D005562:Formazans; D037341:Fumonisins; D013778:Tetrazolium Salts; D017392:Thiobarbituric Acid Reactive Substances; D014255:Trichothecenes; C079782:MTT formazan; D009499:Neutral Red; C056933:fumonisin B1; D008315:Malondialdehyde; D015025:Zearalenone; C007262:deoxynivalenol