The development of a cell-based model for the assessment of carcinogenic potential upon long-term PM2.5 exposure

Shen Chen, Daochuan Li, Haiyan Zhang, Dianke Yu, Rui Chen, Bin Zhang, Y. Tan, Yong Niu, Huawei Duan, Bixian Mai, Shejun Chen, Jianzhen Yu, Tiangang Luan, Liping Chen, Xiumei Xing, Q. Li, Yongmei Xiao, Guanghui Dong, Y. Niu, Michael AschnerRong Zhang, Y. Zheng, Wen Chen

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

To assess the carcinogenic potential of PM2.5 exposure, we developed a cell-based experimental protocol to examine the cell transformation activity of PM2.5 samples from different regions in China. The seasonal ambient PM2.5 samples were collected from three megacities, Beijing (BJ), Wuhan (WH), and Guangzhou (GZ), from November 2016 to October 2017. The mean concentrations of PM2.5 were much higher in the winter season (BJ: 109.64 μg/m3, WH: 79.99 μg/m3, GZ: 49.99 μg/m3) than that in summer season (BJ: 42.40 μg/m3, WH: 25.82 μg/m3, GZ: 19.82 μg/m3). The organic extracts (OE) of PM2.5 samples from combined summer (S) (June, July, August) or winter (W) (November, December, January) seasons were subjected to characterization of chemical components. We treated human bronchial epithelial (HBE) cells expressing CYP1A1 (HBE-1A1) with PM2.5 samples at doses ranging from 0 to 100 μg/mL (0, 1.563, 3.125, 6.25, 12.5, 25, 50, 100 μg/mL) and determined the phenotype of malignant cell transformation. A dose-response relationship was analyzed by benchmark dose (BMD) modeling, and the potential were indicated by BMDL10. The order of the carcinogenic risk of seasonal PM2.5 samples from high to low was BJ-W, WH-W, GZ-W, WH-S, BJ-S, and GZ-S. Notably, we found that the alteration in the lung cancer-related biomarkers, KRAS, PTEN, p53, c-Myc, PCNA, pAKT/AKT, and pERK/ERK was congruent with the activity of cell transformation and the content of specific components of polycyclic aromatic hydrocarbon (PAHs) bound to PM2.5. Taken together, we have successfully developed a cell-based alternative model for the evaluation of potent carcinogenicity upon long-term PM2.5 exposure.

Original languageEnglish (US)
Article number104943
JournalEnvironment International
Volume131
DOIs
StatePublished - Oct 2019

Keywords

  • BMDL
  • Carcinogenic potential
  • Cell transformation
  • Human bronchial epithelial cells
  • P450 CYP1A1
  • Particulate matter

ASJC Scopus subject areas

  • Environmental Science(all)

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