Carbonyl compounds in the gas phase are critical determinants of wood smoke toxicity
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 system. 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, to drive adverse effects. Transcriptional profiling and biochemical analysis of human lung cells exposed at the air-liquid-interface determined the 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 important health hazard. Overall design: Exposure of two human lung cell lines (A549 alveolar epithelial cells, and BEAS-2B bronchial epithelial cells) to three different conditions:  complete wood smoke, filtered wood smoke and control. All conditions were performed in triplicates and analyzed by mRNAseq (Illumina)