Chronic dietary exposure of zebrafish to PAH mixtures results in carcinogenic but not genotoxic effects
2014
Larcher, Thibaut | Perrichon, P. | Vignet, Caroline | Ledevin, Mireille | Le Menach, K. | Lyphout, L. | Landi, L. | Clerandeau, C. | Le Bihanic, F. | Menard, D. | Burgeot, T. | Budzinski, H. | Akcha, F. | Cachot, J. | Cousin, Xavier | Physiopathologie Animale et bioThérapie du muscle et du système nerveux (PAnTher) ; Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS) | PRES Université Nantes Angers Le Mans (UNAM) | École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS) | LIttoral ENvironnement et Sociétés (LIENSs) ; La Rochelle Université (ULR)-Centre National de la Recherche Scientifique (CNRS) | Laboratoire d'Écotoxicologie (LEX) ; Biogéochimie et Ecotoxicologie (BE) ; Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER) | Environnements et Paléoenvironnements OCéaniques (EPOC) ; Observatoire aquitain des sciences de l'univers (OASU) ; Université Sciences et Technologies - Bordeaux 1 (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1 (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École Pratique des Hautes Études (EPHE) ; Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS) | Laboratoire de Physiologie et Génomique des Poissons (LPGP) ; Institut National de la Recherche Agronomique (INRA)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) | ANR ConPhyPop (2009-002) ; Région Poitou-Charentes ; Ifremer ; Conseil Général de Charente-Maritime ; Ministère de l'Enseignement Supérieur de la Recherche
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous contaminants that can be present at high levels as mixtures in polluted aquatic environments. Many PAHs are potent mutagens and several are well-known carcinogens. Despite numerous studies on individual compounds, little is known about the toxicity of PAHs mixtures that are encountered in environmental situations. In the presentwork, zebrafish were continuously fed from 5 days post-fertilisation to 14 months post-fertilisation (mpf) with a diet spiked with fractions of either pyrolytic (PY), petrogenic light oil (LO), or petrogenic heavy oil (HO) origin at three concentrations. A decrease in survival was identified after 3 mpf in fish fed with the highest concentration of HO or LO, but not for PY. All PAH fractions caused preneoplastic and neoplastic disorders in longterm-exposed animals. Target tissues were almost exclusively of epithelial origin, with the bile duct epithelium being themost susceptible to chronic exposure to all PAH fractions, and with germ cells being the second most responsive cells. Significantly higher incidences of neoplasms were observed with increasing PAH concentration and exposure duration. Themost severe carcinogenic effects were induced by dietary exposure to HO compared to exposure to LO or PY (45, 30 and 7 %, respectively, after 9 to 10 months of exposure to an intermediate concentration of PAHs). In contrast, earliest carcinogenic effects were detected as soon as 3 mpf after exposure to LO, including the lowest concentration, or to PY. PAHbioactivation and genotoxicity in blood was assessed by ethoxyresorufin-Odeethylase activity quantification and comet and micronuclei assays, respectively, but none of these were positive. Chronic dietary exposure of zebrafish to PAH mixtures results in carcinogenotoxic events that impair survival and physiology of exposed fish.
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