Génotoxicité comparée de particules atmosphériques PM2.5en fonction de leur origine industrielle, urbaine ou rurale

Abstract

Numerous epidemiological studies have demonstrated a positive correlation between an elevation of Particulate Matter (PM) concentration in ambient air and both mortality and morbidity by cardio-pulmonary diseases. However, mechanism by which PM composition is linked to toxic effects is still unclear. In this context, the present work consisted in an assessment of the metabolic activation of organic fraction and the genotoxic potential of PM2.5 samples collected in Dunkerque city, a French seaside city characterized by intense industrial activity and heavy motor vehicle traffic. 6 PM2.5 samples were collected either under industrial, urban or rural influence, during spring and summer 2008 or autumn and winter 2008-2009. Each of these samples was subjected to an extensive physical (i.e. size distribution, specific area) and chemical characterization (i.e. determination of content in polycyclic aromatic hydrocarbons, polychloro-dibenzo-p-dioxins/furans, polycholorobiphenyls, and metals). Toxicological evaluation subsequently was carried out in vitro on the metabolically competent BEAS-2B cell line. Metabolic activation of PM 2.5 organic fraction was evaluated through the analysis of CYP1A1 induction and CYP1A1 activity, whereas PM genotoxic potential was studied using four complementary methods: Ames test on 3 Salmonella typhimurium tester strains (TA98, TA102, and YG1041), 32P post-labelling of bulky DNA-adducts, comet assay, and micronucleus formation assay. Ames test revealed a significant mutagenicity of all PM2.5 samples, especially on the YG1041 tester strain which is sensitive to nitro-aromatic compounds. Secondly, CYP1A1 gene induction and activity studies showed a strong induction of this enzyme following exposure to PM samples. 32P post-labeling method revealed bulky DNA adducts formation that seemed to be partially linked to polycyclic aromatic hydrocarbons. Furthermore, comet assay demonstrated DNA breakage formation in exposed cells. Finally, micronucleus assay showed an increase in abnormal segregation and/or chromosome breakage after cells' exposure to PM2.5 samples. Genotoxic alterations revealed in this study seem to be linked to both organic and inorganic fractions of PM2.5, whatever the sampling site and period. Altogether, these results give answers about physio-pathological mechanisms that may be involved in PM2.5 genotoxic effects.