Evidences of genotoxic properties of oxy-PAHs and aldehydes using DNA adducts as a contribution to cancer etiology comprehension in exposome context

Abstract : Causes of cancer remain largely unknown in many cases. The part attributable to environmental factors in cancer aetiology is evaluated to 35 %. The synergetic role of multiple environmental factors including for example exposition to environmental pollutants, eating habits, inflammatory or chronic diseases is undoubtedly deeply involved in cancer appearance. These global factors to which an individual is exposed throughout its lifetime is called exposome. Assessing the effects and risks resulting from genotoxic compounds is thus extremely challenging since environmental and endogenous exposures involve complex mixtures of compounds usually present at very low concentrations. Monitoring relevant biomarkers of the internal dose of genotoxic compounds is thus a convenient way to better quantify risks associated to exposures. DNA adducts are biomarkers of genotoxicity both for exposure and precocious effects and are often thought in relation with cancer risk assessment. We focus our efforts on two genotoxic compounds families, namely oxy-PAHs and aldehydes. PAHs are widely distributed pollutants in the environment because of an increasing release, persistence and bioaccumulation potential. Early researches recognized that some PAH derivatives showed higher mutagenic activity, number of these derivatives don’t need any activation to become mutagenic. Oxygenated PAH (oxy-PAHs) have been broadly detected in the environment but their genotoxicity and mutagenicity are poorly documented. A set of 5 oxy-PAHs have been selected in this study. In parallel effects of oxidative stress and indoor pollution on the exposure to 6 aldehydes were studied. DNA adducts were detected for both families congeners and in vitro studies were used to highlight their genotoxity.