Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Av. San Fernando No. 22, Col Sección XVI. C.P. 14080. Delegación Tlalpan, México, D.F., Mexico.
Department of Paediatrics, University of Alberta, 3-591 ECHA, 11405 87th Ave, NW, Edmonton T6G 1C9, Canada.
Environ Pollut. 2015 Aug;203:175-182. doi: 10.1016/j.envpol.2015.03.051. Epub 2015 Apr 20.
The carcinogenic potential of urban particulate matter (PM) has been partly attributed to polycyclic aromatic hydrocarbons (PAHs) content, which activates the aryl hydrocarbon receptor (AhR). Here we report the effect of PM with an aerodynamic size of 10 μm (PM10) on the induction of AhR pathway in A549 cells, evaluating its downstream targets CYP1B1, IL-6, IL-8 and c-Jun. Significant increases in CYP1B1 protein and enzyme activity; IL-6 and IL-8 secretion and c-Jun protein were found in response to PM10. The formation of PAH-DNA adducts was also detected. The involvement of AhR pathway was confirmed with Resveratrol as AhR antagonist, which reversed CYP1B1 and c-Jun induction. Nevertheless, in IL-6 and IL-8 secretion, the Resveratrol was ineffective, suggesting an effect independent of this pathway. Considering the role of c-Jun in oncogenesis, its induction by PM may be contributing to its carcinogenic potential through induction of AhR pathway by PAHs present in PM10.
城市颗粒物（PM）的致癌潜能部分归因于多环芳烃（PAHs）含量，其可激活芳香烃受体（AhR）。在这里，我们报告了空气动力学直径为 10 μm（PM10）的 PM 对 A549 细胞中 AhR 通路的诱导作用，评估了其下游靶标 CYP1B1、IL-6、IL-8 和 c-Jun。PM10 可显著增加 CYP1B1 蛋白和酶活性；IL-6 和 IL-8 的分泌以及 c-Jun 蛋白。还检测到 PAH-DNA 加合物的形成。AhR 拮抗剂白藜芦醇的应用证实了 AhR 通路的参与，其可逆转 CYP1B1 和 c-Jun 的诱导。然而，在 IL-6 和 IL-8 的分泌中，白藜芦醇无效，表明存在 AhR 通路之外的作用机制。考虑到 c-Jun 在致癌作用中的作用，其通过 PM10 中存在的 PAHs 诱导 AhR 通路的诱导，可能对其致癌潜能有贡献。
