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Abstract：
BACKGROUND: 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.
RESULTS: 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.
CONCLUSIONS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：暴露于空气污染固有的化学混合物，已被证明与乳腺癌和肺癌的风险有关。然而,研究暴露于这些污染物混合物的分子机制，如碳氢化合物，在乳腺癌和肺癌的发展中很少见。我们利用硅毒理基因组分析来阐明与两种癌症相关的分子途径，这些途径受暴露于选定碳氢化合物混合物的影响。使用比较毒理基因组学数据库和Cytoscape软件进行数据挖掘和可视化。
结果：25种碳氢化合物，常见的空气污染，致癌性分类为1A/B或2（已知/推测或疑似人类致癌物），分为三类：烷烃和烯烃，卤代烃,和多芳烃。计算机数据挖掘显示，与大多数研究的碳氢化合物通常相互作用的87和44个基因与乳腺癌和肺癌有关。分别。常见基因之间的显性相互作用是共表达，物理互动，遗传相互作用，共同本地化，和共享蛋白质结构域中的相互作用。在这些基因中,在两种癌症的发展中只有16种是常见的。苯并（a）芘和四氯二苯并二恶英与所有16个基因相互作用。被研究的碳氢化合物可能影响的分子途径包括芳香烃受体，化学致癌作用，铁性凋亡,流体剪切应力和动脉粥样硬化，白细胞介素17信号通路，脂质和动脉粥样硬化，NRF2途径，和氧化应激反应。
结论：在硅毒性基因组学工具的固有局限性内，我们阐明了与可能受碳氢化合物混合物影响的乳腺癌和肺癌发展相关的分子途径。我们的发现表明，对氧化应激和炎症损伤的适应性反应在两种癌症的发展中起着重要作用。此外,铁凋亡-由脂质过氧化和铁稳态驱动的非凋亡性程序性细胞死亡-被确定为这些反应的新参与者。最后,AHR可能参与调节IL-8，IL-8是介导乳腺癌侵袭和转移到肺的关键基因，也突出了。更深入地了解与这些途径相关的基因之间的相互作用，和本研究中确定的其他生存信号通路，将为评估吸入接触碳氢化合物混合物的风险提供宝贵的知识。这些发现为未来的体内和体外实验室研究提供了见解，这些研究侧重于吸入暴露于碳氢化合物混合物。
结果：25种碳氢化合物，常见的空气污染，致癌性分类为1A/B或2（已知/推测或疑似人类致癌物），分为三类：烷烃和烯烃，卤代烃,和多芳烃。计算机数据挖掘显示，与大多数研究的碳氢化合物通常相互作用的87和44个基因与乳腺癌和肺癌有关。分别。常见基因之间的显性相互作用是共表达，物理互动，遗传相互作用，共同本地化，和共享蛋白质结构域中的相互作用。在这些基因中,在两种癌症的发展中只有16种是常见的。苯并（a）芘和四氯二苯并二恶英与所有16个基因相互作用。被研究的碳氢化合物可能影响的分子途径包括芳香烃受体，化学致癌作用，铁性凋亡,流体剪切应力和动脉粥样硬化，白细胞介素17信号通路，脂质和动脉粥样硬化，NRF2途径，和氧化应激反应。
结论：在硅毒性基因组学工具的固有局限性内，我们阐明了与可能受碳氢化合物混合物影响的乳腺癌和肺癌发展相关的分子途径。我们的发现表明，对氧化应激和炎症损伤的适应性反应在两种癌症的发展中起着重要作用。此外,铁凋亡-由脂质过氧化和铁稳态驱动的非凋亡性程序性细胞死亡-被确定为这些反应的新参与者。最后,AHR可能参与调节IL-8，IL-8是介导乳腺癌侵袭和转移到肺的关键基因，也突出了。更深入地了解与这些途径相关的基因之间的相互作用，和本研究中确定的其他生存信号通路，将为评估吸入接触碳氢化合物混合物的风险提供宝贵的知识。这些发现为未来的体内和体外实验室研究提供了见解，这些研究侧重于吸入暴露于碳氢化合物混合物。
