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HAP oxydés : étude des effets génotoxiques in-vitro et caractérisation des adduits à l'ADN par spectrométrie de masse

Abstract : DNA adducts are considered as particularly relevant biomarkers of genotoxicity because they are specific of the structure of the genotoxic compound. Our research is focused on genotoxicity studies which encompass alteration of DNA in connection with cancer risk focusing on polycyclic aromatic hydrocarbons (PAHs) derivatives. Studies about toxicity have demonstrated that oxygenated-PAHs (oxy-PAHs) and nitrated-PAHs (nitro-PAHs) were responsible of a large part of the total PAHs toxicity. This work focuses on oxy-PAHs because, although they are ubiquitous compounds in the environment, they still remain largely under studied in terms of toxicity. A set of 7 priority oxy-PAHs, was selected based on criteria of occurrence in the environment and possible toxicity for humans.In order to assess the mutagenic and genotoxic potential of the selected oxy-PAHs, 2’-deoxyguanosine (2’-dG), calf thymus DNA, and immortalized human bronchial epithelial cells (BEAS-2B) were exposed to these molecules. Adducts were detected in post-labelling with phosphorus 32 and were identified and characterized by mass spectrometry. These results prove for the first time, the spontaneous and direct interaction between DNA and at least 3 of our 7 oxy-PAHs. In addition, several cytotoxicity and mutagenicity assays were carried out: MTS assay, CellToxTM Green assay, and Ames assay. This study demonstrated the cytotoxic and mutagenic properties of these oxy-PAHs.
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  • HAL Id : tel-02521475, version 2

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Adeline Clergé. HAP oxydés : étude des effets génotoxiques in-vitro et caractérisation des adduits à l'ADN par spectrométrie de masse. Toxicologie. Normandie Université, 2019. Français. ⟨NNT : 2019NORMC432⟩. ⟨tel-02521475v2⟩

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