Search

• Cell-based bioassays were applied to assess diverse toxic potencies of PM2.5. • BMD modeling was useful in interpretation of concentration-response effects. • Health risk was calculated by toxic potencies and lung deposited dose. The determination of PM 2.5 -induced biological response is essential for understanding the adverse health risk associated with PM 2.5 exposure. In this study, we conducted cell-based bioassays to measure the toxic effects of PM 2.5 exposure, including cytotoxicity, oxidative stress, genotoxicity and inflammatory response. The concentration-response relationship was analyzed by benchmark dose (BMD) modeling and the BMDL 10 was used to estimate the biological potency of PM 2.5 exposure. PM 2.5 samples were collected from three typical megacities of China (Beijing, BJ; Wuhan, WH; Guangzhou, GZ) in typical seasons (winter and summer). The total PM, water-soluble fractions (WSF), and organic extracts (OE) were prepared and subjected to examination of toxic effects. The biological potencies for cytotoxicity, oxidative stress and genotoxicity were generally higher in winter samples, while the inflammatory potency of PM 2.5 was higher in summer samples. The relative health risk (RHR) was determined by integration of the biological potencies and the cumulative exposure level, and the ranks of RHR were BJ-W > WH-W > BJ-S > WH-S > GZ-W > GZ-S. Notably, we note that different PM 2.5 compositions were associated with distinct biological effects, and the health effects distribution of PM 2.5 varied in regions and seasons. These findings demonstrate that the approach of integrated cell-based bioassays could be used for the evaluation of health effects of PM 2.5 exposure. [ABSTRACT FROM AUTHOR]

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 BMDL 10. 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. Unlabelled Image • Human cell-based model was developed to assess the carcinogenic potential of PM2.5. • BMD modeling was used for delineating cell transformation activity of PM2.5 OEs. • Cancer biomarkers altered in concert with the activity of malignant transformation. [ABSTRACT FROM AUTHOR]