流行病学研究确认空气污染是人类患病和死亡的主要原因之一，主要对心血管和呼吸系统产生有害影响。肺部损伤会导致多种严重疾病，如纤维化、慢性阻塞性肺疾病和癌症。有害的环境气溶胶由气体和颗粒相组成，代表了由数百种化合物组成的高度复杂的化学混合物。尽管一些关键的污染物，尤其是颗粒物（PM），可以与不良健康效应相关联，但对相关生物机制和有害气溶胶成分的全面理解仍然不足。在这里，我们采用了一种系统毒理学方法，重点研究了空气污染的重要来源之一——木材燃烧，并证明了气相，特别是醛类，在产生不良效应中起到了关键作用。通过对人类肺细胞在空气液体界面暴露后进行转录谱分析和生化分析，确定了DNA损伤和应激反应以及细胞代谢紊乱作为主要关键事件。连接性映射显示，木烟烟雾和引发DNA-蛋白交联（DPCs）的物质引发的基因表达特征非常相似。实际上，木烟中检测到多种有害醛类物质，这些物质会促进DPCs的形成，引发类似的基因组响应，并导致由木烟引发的DNA损伤。因此，系统毒理学可以发现复杂混合物（如气溶胶）中关键成分，并突显了醛类物质在颗粒物之上作为重要的健康危害因素的作用。© 2023年作者。由Elsevier Ltd.出版。版权所有。

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.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.