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家用煤燃烧产生的细颗粒物中多环芳烃化合物对表皮生长因子受体突变体的体外反应的影响。

Effects of polycyclic aromatic compounds in fine particulate matter generated from household coal combustion on response to EGFR mutations in vitro.

机构信息

Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong; Shenzhen Municipal Key Laboratory for Health Risk Analysis, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.

Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

出版信息

Environ Pollut. 2016 Nov;218:1262-1269. doi: 10.1016/j.envpol.2016.08.084. Epub 2016 Sep 6.

DOI:10.1016/j.envpol.2016.08.084
PMID:27613327
Abstract

Induction of PM-associated lung cancer in response to EGFR-tyrosine kinase inhibitors (EGFR-TKI) remains unclear. Polycyclic aromatic hydrocarbons (PAHs) and their polar derivatives (oxygenated PAHs: OPAHs and azaarenes: AZAs) were characterized in fine particulates (PM) emitted from indoor coal combustion. Samples were collected in Xuanwei (Yunnan Province), a region in China with a high rate of lung cancer. Human lung adenocarcinoma cells A549 (with wild-type EGFR) and HCC827 (with EGFR mutation) were exposed to the PM, followed by treatment with EGFR-TKI. Two samples showed significant and dose-dependent reduction in the cell viability in A549. EGFR-TKI further demonstrated significantly decreased in cell viability in A549 after exposure to the coal emissions. Chrysene and triphenylene, dibenzo[a,h]anthracene, benzo[ghi]perylene, azaarenes and oxygenated polycyclic aromatic hydrocarbons (carbonyl-OPAHs) were all associated with EGFR-TKI-dependent reduced cell viability after 72-h exposure to the PM. The findings suggest the coal emissions could influence the response of EGFR-TKI in lung cancer cells in Xuanwei.

摘要

EGFR 酪氨酸激酶抑制剂(EGFR-TKI)诱导的 PM 相关肺癌仍不清楚。多环芳烃(PAHs)及其极性衍生物(含氧多环芳烃:OPAHS 和氮杂芳烃:AZAs)在室内燃煤排放的细颗粒物(PM)中进行了表征。该研究在云南省宣威市(肺癌高发地区)进行,采集了样本。人类肺腺癌细胞 A549(具有野生型 EGFR)和 HCC827(具有 EGFR 突变)暴露于 PM 后,用 EGFR-TKI 进行处理。有两个样本显示 A549 细胞活力明显且呈剂量依赖性降低。暴露于煤烟排放物后,EGFR-TKI 进一步显著降低了 A549 细胞的活力。苊烯和苊、二苯并[a,h]蒽、苯并[ghi]苝、氮杂芳烃和含氧多环芳烃(羰基-OPAHS)均与 PM 暴露 72 小时后 EGFR-TKI 依赖性降低细胞活力有关。研究结果表明,宣威的煤烟排放可能会影响 EGFR-TKI 在肺癌细胞中的作用。

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