Chronic dietary exposure of zebrafish to PAH mixtures results in carcinogenic but not genotoxic effects

Type Article
Date 2014-12
Language English
Author(s) Larcher Thibaut1, 2, Perrichon Prescilla3, 4, 5, Vignet Caroline3, Ledevin Mireille1, 2, Le Menach Karyn6, Lyphout Laura3, Landi Laure6, Clerandeau Christelle6, Lebihanic F.6, Menard Dominique7, Burgeot Thierry7, Budzinski Helene6, Akcha Farida7, Cachot J.6, Cousin XavierORCID3, 8
Affiliation(s) 1 : INRA, UMR APEX 703, F-44307 Nantes, France.
2 : LUNAM Univ, Ecole Natl Vet Agroalimentaire & Alimentat Nante, F-44307 Nantes, France.
3 : IFREMER, Lab Ecotoxicol, F-17137 Lhoumeau, France.
4 : Univ la Rochelle, Littoral Environm & Soc LIENSs, F-17042 La Rochelle, France.
5 : Univ La Rochelle, CNRS, IFREMER, Federat Rech Environm Dev Durable, F-17000 La Rochelle, France.
6 : Univ Bordeaux, UMR EPOC 5805, F-33405 Talence, France.
7 : IFREMER, Lab Ecotoxicol, F-44311 Nantes, France.
8 : INRA, Lab Physiol & Genom Poissons, F-35042 Rennes, France.
Source Environmental Science And Pollution Research (0944-1344) (Springer Heidelberg), 2014-12 , Vol. 21 , N. 24 , P. 13833-13849
DOI 10.1007/s11356-014-2923-7
WOS© Times Cited 21
Keyword(s) Polycyclic aromatic hydrocarbon, Zebrafish, Carcinogenesis, Genotoxicity, Neoplasia, Carcinoma, Toxicological pathology

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 present work, 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 long-term-exposed animals. Target tissues were almost exclusively of epithelial origin, with the bile duct epithelium being the most 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. The most 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. PAH bioactivation and genotoxicity in blood was assessed by ethoxyresorufin-O-deethylase 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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Larcher Thibaut, Perrichon Prescilla, Vignet Caroline, Ledevin Mireille, Le Menach Karyn, Lyphout Laura, Landi Laure, Clerandeau Christelle, Lebihanic F., Menard Dominique, Burgeot Thierry, Budzinski Helene, Akcha Farida, Cachot J., Cousin Xavier (2014). Chronic dietary exposure of zebrafish to PAH mixtures results in carcinogenic but not genotoxic effects. Environmental Science And Pollution Research, 21(24), 13833-13849. Publisher's official version : , Open Access version :