Volatile organic compounds (VOCs) have proven to be hazardous to the human respiratory system. However, the underlying biological mechanisms remain poorly understood. Therefore, targeted determination of eleven VOC metabolites (mVOCs) along with the nontargeted metabolomic analysis was performed on urine samples collected from lung cancer patients and healthy individuals. Nine mVOCs mainly derived from aldehydes, alkenes, amides, and aromatics were detected in > 90 % of the urine samples, suggesting that the participants were ubiquitously exposed to these typical VOCs. A molecular gatekeeper discovery workflow was employed to link the exposure biomarkers with correlated clusters of endogenous metabolites. As a result, multiple metabolic pathways, including amino acid metabolism, steroid hormone biosynthesis and metabolism, and fatty acid β-oxidation were connected with VOC exposure. Furthermore, 16 of 73 molecular gatekeepers were associated with lung cancer and pointed to a few disrupted metabolic pathways related to hydroxysteroids and acylcarnitine. The shift in molecular profiles was validated in rat model post VOC administration. Thereinto, the up-regulation of enzymes involved in acylcarnitine synthesis and transport in rat lung tissues highlighted that the mitochondrial dysfunction may be a potential carcinogenic mechanism. Our findings provide new insights into the mechanisms underlying lung cancer induced by VOC exposure.

中文翻译：

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与肺癌相关的挥发性有机化合物暴露：通过代谢组学了解作用机制


挥发性有机化合物 （VOC） 已被证明对人体呼吸系统有害。然而，潜在的生物学机制仍然知之甚少。因此，对从肺癌患者和健康个体收集的尿液样本进行了 11 种 VOC 代谢物 （mVOCs） 的靶向测定和非靶向代谢组学分析。在 > 90% 的尿液样本中检测到 9 种主要来源于醛、烯烃、酰胺和芳烃的 mVOC，这表明参与者普遍暴露于这些典型的 VOCs。采用分子守门人发现工作流程将暴露生物标志物与相关的内源性代谢物簇联系起来。结果，多种代谢途径，包括氨基酸代谢、类固醇激素生物合成和代谢以及脂肪酸β氧化与 VOC 暴露有关。此外，73 个分子守门人中有 16 个与肺癌有关，并指出一些与羟基类固醇和酰基肉碱相关的代谢途径被破坏。在 VOC 给药后的大鼠模型中验证了分子谱的变化。其中，大鼠肺组织中参与酰基肉碱合成和转运的酶的上调突出表明线粒体功能障碍可能是一种潜在的致癌机制。我们的研究结果为 VOC 暴露诱导肺癌的潜在机制提供了新的见解。