The combined effects of physicochemical properties of size-fractionated ambient particulate matter on in vitro toxicity in human A549 lung epithelial cells

Umme S Akhtar; Neeraj Rastogi; Robert D McWhinney; Bruce Urch; Chung-Wai Chow; Greg J Evans; Jeremy A Scott

doi:10.1016/j.toxrep.2014.05.002

The combined effects of physicochemical properties of size-fractionated ambient particulate matter on in vitro toxicity in human A549 lung epithelial cells

Toxicol Rep. 2014 May 16:1:145-156. doi: 10.1016/j.toxrep.2014.05.002. eCollection 2014.

Authors

Umme S Akhtar^{1

2}, Neeraj Rastogi^{1

2}, Robert D McWhinney^{2

3}, Bruce Urch^{2

4}, Chung-Wai Chow^{2

5

6}, Greg J Evans^{1

2

4

7

8}, Jeremy A Scott^{2

4

5

7

9}

Affiliations

¹ Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada.
² Southern Ontario Centre for Atmospheric Aerosol Research (SOCAAR), Toronto, Ontario, Canada.
³ Department of Chemistry, University of Toronto, Toronto, Ontario, Canada.
⁴ Gage Occupational & Environmental Health Unit, St. Michael's Hospital, Toronto, Ontario, Canada.
⁵ Institute of Medical Science, Faculty of Medicine, University of Toronto, Ontario, Canada.
⁶ Division of Respirology and Multi-Organ Transplantation Programme, University Health Network, Department of Medicine, University of Toronto, Ontario, Canada.
⁷ Division of Occupational and Environmental Health, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
⁸ Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada.
⁹ Department of Health Science, Lakehead University, Division of Medical Sciences, Northern Ontario School of Medicine, Thunder Bay, Ontario, Canada.

Abstract

Epidemiological and toxicological studies have suggested that the health effects associated with exposure to particulate matter (PM) are related to the different physicochemical properties of PM. These effects occur through the initiation of differential cellular responses including: the induction of antioxidant defenses, proinflammatory responses, and ultimately cell death. The main objective of this study was to investigate the effects of size-fractionated ambient PM on epithelial cells in relation to their physicochemical properties. Concentrated ambient PM was collected on filters for three size fractions: coarse (aerodynamic diameter [AD] 2.5-10 μm), fine (0.15-2.5 μm), and quasi-ultrafine (<0.2 μm), near a busy street in Toronto, Ontario, Canada. Filters were extracted and analyzed for chemical composition and redox activity. Chemical analyses showed that the coarse, fine, and quasi-ultrafine particles were comprised primarily of metals, water-soluble species, and organic compounds, respectively. The highest redox activity was observed for fine PM. After exposure of A549 cells to PM (10-100 μg/ml) for 4 h, activation of antioxidant, proinflammatory and cytotoxic responses were assessed by determining the expression of heme oxygenase (HMOX-1, mRNA), interleukin-8 (IL-8, mRNA), and metabolic activity of the cells, respectively. All three size fractions induced mass-dependent antioxidant, proinflammatory, and cytotoxic responses to different degrees. Quasi-ultrafine PM caused significant induction of HMOX-1 at the lowest exposure dose. Correlation analyses with chemical components suggested that the biological responses correlated mainly with transition metals and organic compounds for coarse and fine PM and with organic compounds for quasi-ultrafine PM. Overall, the observed biological responses appeared to be related to the combined effects of size and chemical composition and thus both of these physicochemical properties should be considered when explaining PM toxicity.

Keywords: Ambient particulate matter; Antioxidant enzyme; Cytotoxicity; Inflammation; Physicochemical properties; Reactive oxygen species.