Study of the genotoxicity of 7 oxy-PAHs: focus on DNA adducts
Résumé
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 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 remain still largely under studied in terms of toxicity.
In this study, a panel of 7 oxy-PAHs (1,2-naphthoquinone, 7,12-benzo[a]anthracenequinone, 6H-benzo[cd]pyrene-6-one, 7H-benz[de]anthracene-7-one, 9,10-anthraquinone, 5,12-naphtacenequinone, and 11H-benzo[b]fluoren-11-one) were selected on criteria of occurrence and potential toxicity.
In order to assess the mutagenic and genotoxic potential of the selected oxy-PAHs, 2’-deoxyguanosine (2’-dG), calf thymus DNA, and Human bronchial epithelial cells (BEAS-2B) were exposed to these molecules. Adducts were detected for all exposures and DNA adducts with 2’-dG were identified and characterized. These results prove for the first time, the spontaneous and direct interaction between DNA and these oxy-PAHs. In addition, several cytotoxicity test and mutagenicity assays were carried out: MTS assay, Cell tox Green assay, and Ame’s test. The cytotoxic and mutagenic properties of these oxy-PAHs were demonstrated.