TY - JOUR
T1 - The development of a cell-based model for the assessment of carcinogenic potential upon long-term PM2.5 exposure
AU - Chen, Shen
AU - Li, Daochuan
AU - Zhang, Haiyan
AU - Yu, Dianke
AU - Chen, Rui
AU - Zhang, Bin
AU - Tan, Y.
AU - Niu, Yong
AU - Duan, Huawei
AU - Mai, Bixian
AU - Chen, Shejun
AU - Yu, Jianzhen
AU - Luan, Tiangang
AU - Chen, Liping
AU - Xing, Xiumei
AU - Li, Q.
AU - Xiao, Yongmei
AU - Dong, Guanghui
AU - Niu, Y.
AU - Aschner, Michael
AU - Zhang, Rong
AU - Zheng, Y.
AU - Chen, Wen
N1 - Publisher Copyright:
© 2019 The Authors
PY - 2019/10
Y1 - 2019/10
N2 - 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.
AB - 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.
KW - BMDL
KW - Carcinogenic potential
KW - Cell transformation
KW - Human bronchial epithelial cells
KW - P450 CYP1A1
KW - Particulate matter
UR - http://www.scopus.com/inward/record.url?scp=85068471149&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068471149&partnerID=8YFLogxK
U2 - 10.1016/j.envint.2019.104943
DO - 10.1016/j.envint.2019.104943
M3 - Article
C2 - 31295644
AN - SCOPUS:85068471149
SN - 0160-4120
VL - 131
JO - Environment international
JF - Environment international
M1 - 104943
ER -
