https://doi.org/10.1016/j.envint.2023.108169
Marco Dilger a,b, Olivier Armant b,c, Larissa Ramme a,b, Sonja Mülhopt a,d, Sean C. Sapcariu a,e, Christoph Schlager a,d, Elena Dilger f, Ahmed Reda a,g,h, Jürgen Orasche a,g,h, Jürgen Schnelle-Kreis a,h, Thomas M. Conlon i, Ali Önder Yildirim a,i, Andrea Hartwig f, Ralf Zimmermann a,g,h, Karsten Hiller a,e, Silvia Diabate a,b, Hanns-Rudolf Paur a,d, Carsten Weiss b
a HICE – Helmholtz Virtual Institute of Complex Molecular Systems in Environmental Health – Aerosols and Health, Germany1
b Institute of Biological and Chemical Systems, Biological Information Processing, Karlsruhe Institute of Technology, Campus North, Eggenstein-Leopoldshafen, Germany
c Institut de Radioprotection et de Suret´e Nucl´eaire (IRSN), PSE-ENV/SRTE/LECO, Cadarache, Saint-Paul-lez-Durance 13115, France
d Institute for Technical Chemistry, Karlsruhe Institute of Technology, Campus North, Eggenstein-Leopoldshafen, Germany
e Luxembourg Centre for Systems Biomedicine, University of Luxembourg, L-4362 Esch-Belval, Luxembourg
f Institute of Applied Biosciences, Department of Food Chemistry and Toxicology, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany
g Joint Mass Spectrometry Centre, Chair of Analytical Chemistry, Institute of Chemistry, University Rostock, Germany
h Joint Mass Spectrometry Centre, CMA – Comprehensive Molecular Analytics, Helmholtz Zentrum München, Neuherberg, Germany
i Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Neuherberg, Germany
Abstract
Epidemiological studies identified air pollution as one of the prime causes for human morbidity and mortality, due to harmful effects mainly on the cardiovascular and respiratory systems. Damage to the lung leads to several severe diseases such as fibrosis, chronic obstructive pulmonary disease and cancer. Noxious environmental aerosols are comprised of a gas and particulate phase representing highly complex chemical mixtures composed of myriads of compounds. Although some critical pollutants, foremost particulate matter (PM), could be linked to adverse health effects, a comprehensive understanding of relevant biological mechanisms and detrimental aerosol constituents is still lacking. Here, we employed a systems toxicology approach focusing on wood combustion, an important source for air pollution, and demonstrate a key role of the gas phase, specifically carbonyls, in driving adverse effects. Transcriptional profiling and biochemical analysis of human lung cells exposed at the air–liquid-interface determined DNA damage and stress response, as well as perturbation of cellular metabolism, as major key events. Connectivity mapping revealed a high similarity of gene expression signatures induced by wood smoke and agents prompting DNA-protein crosslinks (DPCs). Indeed, various gaseous aldehydes were detected in wood smoke, which promote DPCs, initiate similar genomic responses and are responsible for DNA damage provoked by wood smoke. Hence, systems toxicology enables the discovery of critical constituents of complex mixtures i.e. aerosols and highlights the role of carbonyls on top of particulate matter as an important health hazard.
