Génotoxicité des hydrocarbures aromatiques polycycliques adsorbés à la surface dʼun aérosol urbano-industriel ( PM 2 , 5 ) In vitro evaluation of the genotoxicity of polycyclic aromatic hydrocarbons-coated onto airborne PM 2 . 5

Polycyclic aromatic hydrocarbons (PAH) represent a family of chemical compounds including a number of members recognized for their carcinogenicity. Their presence is often detected in mixtures very complex and heterogeneous, such as Particulate Matter (PM). However, the genotoxicity of such aerosols has been rarely studied. To improve the knowledge of the underlying mechanisms of action involved in air pollution Particulate Matter (PM)-induced toxicity in human lungs, a PM sampling was realized in Dunkerque. We were interested in the metabolic activation of Polycyclic Aromatic Hydrocarbons (PAH)-coated onto air pollution PM, and, thereafter, the formation of PAH-DNA adducts in a human lung epithelial cell model (A549 cell line). Cells were exposed to Dunkerque cityʼs PM2.5 at their Lethal Concentrations at 10% and 50% (i.e. LC10 = 23.72 μg/mL or 6.33 μg/cm2, and LC50 = 118.60 μg/mL or 31.63 μg/cm2), and the study of Cytochrome P450 (CYP) 1A1 gene expression (i.e. RT-PCR) and protein activity (i.e. EROD activity), and the formation of PAH-DNA adducts (i.e. 32P-post labelling), were investigated after 24, 48 and 72 h. Negative (i.e. TiO2 or desorbed PM, dPM; EqLC10 = 19.42 μg/mL or 5.18 μg/cm2, and EqLC50 = 97.13 μg/mL or 25.90 μg/cm2), and positive (i.e. benzo(a)pyrene; 1 μM) controls were included in the experimental design. Statistically significant increases of CYP1A1 gene expression and protein activity were observed in A549 cells, 24, 48 and 72 h after their exposure to dPM, suggesting thereby that the employed outgassing method was not efficient enough to remove total PAH. Both the CYP1A1 gene expression and EROD activity were highly induced 24, 48 and 72 h after cell exposure to PM. However, only very low levels of PAH-DNA adducts, also not reliably quantifiable, were reported 72 h after cell exposure to dPM, and, particularly, PM. The relatively low levels of PAH-coated onto Dunkerque Cityʼs PM2.5 could notably contribute to explain the borderline detection of PAH-DNA adducts in dPM and/or PM-exposed A549 cells. We concluded that remaining very low doses of PAH in dPM or relatively low doses of PAH-coated onto PM were involved in enzymatic induction, a key feature in PAH-toxicity, but failed to show a quantitative genotoxicity in the human lung epithelial cell model we used.