Evaluation of genotoxicity and mutagenicity of 1,2-naphthoquinone

International audiencePolycyclic Aromatic Hydrocarbons (PAHs) are pollutants that are widely spread in the environment because of increasing release, persistence, and bioaccumulation potential. Different toxicities have been described depending on compounds of interest, either alone and less frequently as mixtures. Recently, some studies have demonstrated that derivatives of PAHs, like oxygenated-PAHs (oxy-PAHs), are responsible of a part of the toxicity attributed to PAHs. Oxy-PAHs are very present in contaminated environment but remain still poorly studied concerning inherent toxicity. Number of these oxy-PAHs are otherwise product by metabolism of living organisms.Naphthalene is a compound of PAHs family and has been classified in 2002 as possible carcinogenic compound for human by the International Agency for Research on Cancer (IARC). As most of carcinogenic compounds, toxicity of naphthalene depends of its metabolic activation. Several enzymatic activation pathways yield to reactive metabolites like 1,2-naphthoquinone (1,2-NphQ), an oxygenated derivative of the parent compound. 1,2-NphQ is an electrophilic compound and thus may be bind to nucleophilic compounds such as RNA or DNA and potentially formed adducts. In order to evaluate the genotoxic and mutagenic potential of 1,2-NphQ, epithelial cells from human bronchial epithelium (BEAS-2B) were exposed to this molecule. A first research of DNA adducts has been realized thanks to the ultrasensitive 32P-postlabelling assay. In order to develop a complementary method in mass spectrometry, the synthesis and purification of analytical standards obtained from reaction of 1,2-NphQ and 2’-deoxyguanosine has been realized. Moreover, mutagenicity of 1,2-NphQ has been evaluated thanks to Ames assay