Lung developmental is altered after inhalation exposure to various concentrations of calcium arsenate
AffiliationDepartment of Cellular & Molecular Medicine, University of Arizona College of Medicine
Department of Pharmacology and Toxicology, University of Arizona College of Pharmacy
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CitationChau, B., Witten, M. L., Cromey, D., Chen, Y., & Lantz, R. C. (2021). Lung developmental is altered after inhalation exposure to various concentrations of calcium arsenate. Toxicology and Applied Pharmacology.
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AbstractExposure to dust from active and abandoned mining operations may be a very significant health hazard, especially to sensitive populations. We have previously reported that inhalation of real-world mine tailing dusts during lung development can alter lung function and structure in adult male mice. These real-world dusts contain a mixture of metal(loid)s, including arsenic. To determine whether arsenic in inhaled dust plays a role in altering lung development, we exposed C57Bl/6 mice to a background dust (0 arsenic) or to the background dust containing either 3% or 10% by mass, calcium arsenate. Total level of exposure was kept at 100 μg/m3. Calcium arsenate was selected since arsenate is the predominant species found in mine tailings. We found that inhalation exposure during in utero and postnatal lung development led to significant increases in pulmonary baseline resistance, airway hyper-reactivity, and airway collagen and smooth muscle expression in male C57Bl/6 mice. Responses were dependent on the level of calcium arsenate in the simulated dust. These changes were not associated with increased expression of TGF-β1, a marker of epithelial to mesenchymal transition. However, responses were correlated with decreases in the expression of club cell protein 16 (CC16). Dose-dependent decreases in CC16 expression and increases in collagen around airways was seen for animals exposed in utero only (GD), animals exposed postnatally only (PN) and animals continuously exposed throughout development (GDPN). These data suggest that arsenic inhalation during lung development can decrease CC16 expression leading to functional and structural alterations in the adult lung.
Note12 month embargo; available online 9 October 2021
VersionFinal accepted manuscript