Étude des voies de bioactivation du benzo[a]pyrène et du fluoranthène chez la sole commune (Solea solea) : Profil métabolique et génotoxicité, Study of the bioactivation pathways of benzo[a]pyrene and fluoranthene on the common sole (Solea solea): metabolic profile and genotoxicity

The aim of this Ph‟D was to study the biotransformation and the genotoxicity of two PAH of interest, namely the benzo[a]pyrene (BaP) and the fluoranthene (Fluo), in the common sole Solea solea, which is a benthic species sensitive to chemical pollution. The use of in vitro exposure models and the application of two different chemical analytical techniques allowed demonstrating that, as in higher vertebrates, the dihydrodiols and the phenols of BaP and Fluo are the major metabolites produced by sole liver enzymes. In vitro, the genotoxic potential of BaP and Fluo was demonstrated in sole, by the production of DNA adducts and oxidative DNA damage. The genotoxicity of Fluo appeared to be 50 fold less important than the genotoxicity of BaP. In the case of BaP, three adducts produced in sole following microsomal activation have been identified by mass spectrometry. As in higher vertebrates, these adducts are produced through the diol-epoxide activation pathway. The genotoxicity of an equimolar mixture of PAHs (BaP, Fluo, Pyr) was confirmed in vivo at the individual scale. A correlation was observed between the level of biliary PAH metabolites and the level of oxidative DNA damage. These results showed the ability of sole liver enzymes to metabolise the BaP and the Fluo through similar pathways to those described in higher vertebrates. Indeed, their in vitro and in vivo metabolism occurs through the production of electrophilic metabolites, able to bind to DNA. Several metabolites are able to generate reactive oxygen species causing oxidative DNA damages.