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Modulation de la génotoxicité des hydrocarbures aromatiques polycycliques (HAP) en mélanges

Abstract : Polycyclic Aromatic Hydrocarbons (PAH) are atmospheric pollutants arising from incomplete combustion of organic matter. Residential heating, vehicle exhaust, cigarette smoke and industrial activities are the main sources of PAH in the environment. Some of these PAH are suspected or known carcinogens to humans like benzo[a]pyrene (BaP) which causes DNA damage. Most studies focused on the effect of individual PAH whereas human exposure always occurs through complex mixtures. This work aims at evaluating the modulation in vitro of the genotoxicity of PAH in mixtures, using in a cellular model of human hepatocytes (HepG2). To achieve this goal, biomarkers of genotoxicity such as the comet assay measuring DNA strand breaks, and the HPLC/MS/MS measurement of DNA adducts of BPDE, the most reactive BaP metabolite, were chosen. In a first step, DNA damage induced by BaP as a pure compound or in binary mixture with other particulate PAH were investigated in order to highlight the mode of interaction between these compounds. This study was then extended, in one hand to real atmospheric mixtures collected in the environment or inside industrial plants, and in another hand to the reconstructed corresponding particulate PAH fraction. In a last more applied part, suitability of those in vitro tests for the monitoring of the genotoxic risk associated with ambient air. This work emphasizes the need for a deeper understanding of the mechanisms underlying interactions between compounds, as well as the necessity to use mathematical modelling as a tool in the assessment of human health hazards posed by exposure to ambient air.
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Submitted on : Sunday, February 14, 2010 - 11:33:51 PM
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  • HAL Id : tel-00456384, version 1



Adeline Tarantini. Modulation de la génotoxicité des hydrocarbures aromatiques polycycliques (HAP) en mélanges. Sciences du Vivant [q-bio]. Université Joseph-Fourier - Grenoble I, 2009. Français. ⟨tel-00456384⟩



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