Cytotoxic and Genotoxic Effects of Combustion-Derived Particles from Different Emission Sources

Background and Aims Diesel and Biomass combustion-derived particles (CDPs) largely contribute to air pollution and likely to the adverse health effects observable in the exposed populations. Anyway our knowledge on the different biological responses deriving from the particles emitted from different sources is still poor, as well as the comprehension of the modes of action of such particles with variable physico-chemical properties. This study aims at comparatively investigate the cytoxic and genotoxic properties of particles collected during the combustion of different diesel and biomass sources. Methods Diesel Exhaust ultrafine Particles (DEP) were from two standard references (DEP 1650b and 2975) and directly sampled from a Euro4 vehicle run over a chassis dyno. Biomass-derived combustion particles were collected from the emission of heating systems operating with pellet, charcoal and wood. CDPs were morphologically and chemically characterized. Monocultures of human lung cells and a 3D in vitro model of the alveolar blood barrier (ABB) were used to study the CDP-induced biological effects. Cell viability, inflammatory response, antioxidant and xenobiotic metabolism activity, DNA damage were investigated. Key results of the study DEP exposure of lung cells did not cause significant cell death, but especially DEP Euro4, collected during a standard urban cycle driving, did induce oxidative stress and release of inflammatory cytokines, that were also able to activate endothelial cells. Pellet-derived particles decreased cell viability, inducing necrosis, while charcoal and wood CDPs mainly induced apoptosis. The strongest cytotoxic action was achieved after exposure to CDPs from not-certified pellet in respect to certified pellet and other biomass-derived CDPs. Significant increase of HO-1, the activation of the cytochrome P450 enzymes and DNA strand breaks were observed for all biomass-derived CDPs, confirming the oxidative-mediated genotoxicity as a shared mechanism of action. 3D coculture of alveolar and endothelial cells revealed the ability of subcytotoxic CDP concentrations to induce vascular endothelial dysfunction upon exposure of the alveolar epithelium. Conclusions These results suggest that CDPs from different emission sources may impact at different extent on the respiratory health and can activate different toxicological pathways, pointing out the importance of more specific strategies to lower the health hazard coming from the emission of diesel vehicles and biomass-propelled heating systems. Acknowledgments Fondazione Cariplo (proj. ID 2013-1038); Italian Ministry of Foreign Affairs and International Cooperation( proj. ID PGR00786).