接触空气污染中固有的化学混合物已被证明与乳腺癌和肺癌的风险有关。然而，关于暴露于这些污染物的混合物（例如碳氢化合物）在乳腺癌和肺癌发生过程中的分子机制的研究很少。我们利用计算机毒理学分析来阐明与两种癌症相关的分子途径，这些癌症受暴露于选定碳氢化合物混合物的影响。使用比较毒理学数据库和 Cytoscape 软件进行数据挖掘和可视化。空气污染中常见的 25 种碳氢化合物，其致癌性分类为 1 A/B 或 2（已知/推定或疑似人类致癌物），分为三组：烷烃和烯烃、卤代烃和多环芳烃。计算机数据挖掘显示，与大多数研究的碳氢化合物相互作用的 87 个和 44 个基因分别与乳腺癌和肺癌有关。常见基因之间的主要相互作用是共表达、物理相互作用、遗传相互作用、共定位和共享蛋白质域中的相互作用。在这些基因中，只有 16 个在两种癌症的发展中都是常见的。苯并(a)芘和四氯二苯并二恶英与所有 16 个基因相互作用。所研究的碳氢化合物可能影响的分子途径包括芳基碳氢化合物受体、化学致癌、铁死亡、流体剪切应力和动脉粥样硬化、白细胞介素17信号传导途径、脂质和动脉粥样硬化、NRF2途径和氧化应激反应。在计算机毒物基因组学的固有局限性内工具，我们阐明了与乳腺癌和肺癌发展相关的分子途径，可能受碳氢化合物混合物的影响。我们的研究结果表明，对氧化应激和炎症损伤的适应性反应在这两种癌症的发展中发挥着重要作用。此外，铁死亡（一种由脂质过氧化和铁稳态驱动的非凋亡性程序性细胞死亡）被认为是这些反应中的新参与者。最后，还强调了 AHR 可能参与调节 IL-8（介导乳腺癌侵袭和肺部转移的关键基因）。更深入地了解与这些途径相关的基因之间的相互作用以及本研究中确定的其他生存信号途径，将为评估吸入碳氢化合物混合物的风险提供宝贵的知识。这些发现为未来体内和体外实验室研究提供了见解，这些研究重点关注碳氢化合物混合物的吸入暴露。© 2024。作者。

Exposure to chemical mixtures inherent in air pollution, has been shown to be associated with the risk of breast and lung cancers. However, studies on the molecular mechanisms of exposure to a mixture of these pollutants, such as hydrocarbons, in the development of breast and lung cancers are scarce. We utilized in silico toxicogenomic analysis to elucidate the molecular pathways linked to both cancers that are influenced by exposure to a mixture of selected hydrocarbons. The Comparative Toxicogenomics Database and Cytoscape software were used for data mining and visualization.Twenty-five hydrocarbons, common in air pollution with carcinogenicity classification of 1 A/B or 2 (known/presumed or suspected human carcinogen), were divided into three groups: alkanes and alkenes, halogenated hydrocarbons, and polyaromatic hydrocarbons. The in silico data-mining revealed 87 and 44 genes commonly interacted with most of the investigated hydrocarbons are linked to breast and lung cancer, respectively. The dominant interactions among the common genes are co-expression, physical interaction, genetic interaction, co-localization, and interaction in shared protein domains. Among these genes, only 16 are common in the development of both cancers. Benzo(a)pyrene and tetrachlorodibenzodioxin interacted with all 16 genes. The molecular pathways potentially affected by the investigated hydrocarbons include aryl hydrocarbon receptor, chemical carcinogenesis, ferroptosis, fluid shear stress and atherosclerosis, interleukin 17 signaling pathway, lipid and atherosclerosis, NRF2 pathway, and oxidative stress response.Within the inherent limitations of in silico toxicogenomics tools, we elucidated the molecular pathways associated with breast and lung cancer development potentially affected by hydrocarbons mixture. Our findings indicate adaptive responses to oxidative stress and inflammatory damages are instrumental in the development of both cancers. Additionally, ferroptosis-a non-apoptotic programmed cell death driven by lipid peroxidation and iron homeostasis-was identified as a new player in these responses. Finally, AHR potential involvement in modulating IL-8, a critical gene that mediates breast cancer invasion and metastasis to the lungs, was also highlighted. A deeper understanding of the interplay between genes associated with these pathways, and other survival signaling pathways identified in this study, will provide invaluable knowledge in assessing the risk of inhalation exposure to hydrocarbons mixture. The findings offer insights into future in vivo and in vitro laboratory investigations that focus on inhalation exposure to the hydrocarbons mixture.© 2024. The Author(s).