Abstract
In this study, we used cytotoxicity assays, proteomic and gene expression analyses to examine the difference in response of A549 cells to two silica particles that differ in physical properties, namely cristobalite (CR) and α‐quartz (Min‐U‐Sil 5, MI). Cytotoxicity assays such as lactate dehydrogenase release, 5‐bromo‐2′‐deoxyuridine incorporation and cellular ATP showed that both silica particles could cause cell death, decreased cell proliferation and metabolism in the A549 human lung epithelial cells. While cytotoxicity assays revealed little difference between CR and MI exposures, proteomic and gene expression analyses unveiled both similar and unique molecular changes in A549 cells. For instance, two‐dimensional gel electrophoresis data indicated that the expression of proteins in the cell death (e.g., ALDH1A1, HTRA2 and PRDX6) and cell proliferation (e.g., FSCN1, HNRNPAB and PGK1) pathways were significantly different between the two silica particles. Reverse transcription–polymerase chain reaction data provided additional evidence supporting the proteomic findings. Preliminary assessment of the physical differences between CR and MI suggested that the extent of surface interaction between particles and cells could explain some of the observed biological effects. However, the differential dose–response curves for some other genes and proteins suggest that other physical attributes of particulate matter can also contribute to particulate matter‐related cellular toxicity. Our results demonstrated that toxicoproteomic and gene expression analyses are sensitive in distinguishing subtle toxicity differences associated with silica particles of varying physical properties compared to traditional cytotoxicity endpoints. Copyright © 2016 Her Majesty the Queen in Right of Canada. Journal of Applied Toxicology published by John Wiley & Sons, Ltd.
Highlights
Inhalation of silica has been reported to cause pulmonary fibrosis or silicosis, a condition where scar tissue is formed in the lung (AGN, 1930; Belt, 1930; Cassel et al, 2008)
The scanning electron microscopy (SEM) image in Fig. 1(B) showed that MI particles cover a broad range of sizes
There is a lack of porosity observed on the surface of the particles, which is consistent with a highly crystalline solid sample that has been ground from a larger, non-porous sample
Summary
Inhalation of silica has been reported to cause pulmonary fibrosis or silicosis, a condition where scar tissue is formed in the lung (AGN, 1930; Belt, 1930; Cassel et al, 2008). Data from Cassel et al (2008) and Dostert et al (2008) demonstrated that the inflammatory response depends on the production of reactive oxygen species (ROS), whereas data from Hornung et al (2008) suggested that the production of ROS is not necessary. These discrepancies may arise from the difference in materials and/or the methods used in these studies. The silica particles used in these three studies were 1.5 μm amorphous silicon dioxide (Dostert et al, 2008), Min-
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