Unburned tobacco cigarette smoke alters rat ultrastructural lung airways and DNA

none28siIntroduction: Recently, the Food and Drug Administration (FDA) authorized the marketing of IQOS Tobacco Heating System as a Modified Risk Tobacco Product (MRTP) based on an electronic heat-not-burn technology that purports to reduce the risk. Methods: Sprague-Dawley rats were exposed in a whole-body mode to IQOS aerosol for 4 weeks. We performed the chemical characterization of IQOS mainstream and we studied the ultrastructural changes in trachea and lung parenchyma of rats exposed to IQOS stick mainstream and tissue pro-inflammatory markers. We investigated the reactive oxygen species (ROS) amount along with the markers of tissue and DNA oxidative damage. Moreover, we tested the putative genotoxicity of IQOS mainstream through Ames and alkaline Comet mutagenicity assays. Results: Here, we identified irritating and carcinogenic compounds including aldehydes and polycyclic aromatic hydrocarbons in the IQOS mainstream as sign of incomplete combustion and degradation of tobacco, that lead to severe remodelling of smaller and largest rat airways. We demonstrated that IQOS mainstream induces lung enzymes that activate carcinogens, increases tissue reactive radical concentration; promotes oxidative DNA breaks and gene level DNA damage; and stimulates mitogen activated protein kinase (MAPK) pathway which is involved in the conventional tobacco smoke-induced cancer progression. Conclusions: Collectively, our findings reveal that IQOS causes grave lung damage and promotes factors that increase cancer risk. Implications: IQOS has been proposed as a safer alternative to conventional cigarettes, due to depressed concentration of various harmful constituents typical of traditional tobacco smoke. However, its lower health risks to consumers have yet to be determined. Our findings confirm that IQOS mainstream contains pyrolysis and thermogenic degradation by-products, the same harmful constituents of traditional cigarette smoke, and, for the first time, we show that it causes grave lung damage and promotes factors that increase cancer risk in the animal model.mixedFabio Vivarelli, Donatella Canistro, Silvia Cirillo, Ryan J Elias, Silvia Granata, Matilde Mussoni , Sabrina Burattini , Elisabetta Falcieri , Eleonora Turrini , Carmela Fimognari , Annamaria Buschini , Mirca Lazzaretti , Sofia Beghi , Stefano Girotti, Stefano Sangiorgi , Luca Bolelli , Severino Ghini , Elida Nora Ferri , Ivan Fagiolino , Paola Franchi , Marco Lucarini , Dario Mercatante , Maria Teresa Rodriguez-Estrada , Antonello Lorenzini, Silvia Marchionni , Morena Gabriele , Vincenzo Longo , Moreno PaoliniFabio Vivarelli, Donatella Canistro, Silvia Cirillo, Ryan J Elias, Silvia Granata, Matilde Mussoni , Sabrina Burattini , Elisabetta Falcieri , Eleonora Turrini , Carmela Fimognari , Annamaria Buschini , Mirca Lazzaretti , Sofia Beghi , Stefano Girotti, Stefano Sangiorgi , Luca Bolelli , Severino Ghini , Elida Nora Ferri , Ivan Fagiolino , Paola Franchi , Marco Lucarini , Dario Mercatante , Maria Teresa Rodriguez-Estrada , Antonello Lorenzini, Silvia Marchionni , Morena Gabriele , Vincenzo Longo , Moreno Paolin