Superfund Research Program
Toxicological Impact of Mine Tailings Dust on Lung Epithelial Barrier Function
Project Leader: Robert Clark Lantz
Co-Investigators: Scott Boitano, Donna D. Zhang
Grant Number: P42ES004940
Funding Period: 2005-2020
Project Summary (2017-2020)
Inhalable dusts in the Southwest U.S., especially those found downwind of legacy mine tailings and smelters, can contain high levels of arsenic and other contaminants. It is well established that arsenic exposure occurring via ingestion (primarily drinking water) can result in adverse health effects that prominently include lung disease. Around legacy mines, such as the Iron King Mine and Humboldt Smelter Superfund Site, arsenic exposures can occur via inhalation of aerosolized dusts from the mine tailings or abandoned smelter.
The researcher's previous work with ingested arsenic has demonstrated that exposure can affect airway structure/function in vitro and in vivo. Collectively, data indicate that arsenic exposure compromises the barrier integrity of the airway epithelium by inducing an epithelial to mesenchymal transition (EMT). Such loss of airway epithelial barrier function can lead to reduced innate immunity, increased inflammation, increased exposure of underlying tissue to airway insults, increased airway infection and ultimately, lung disease. While inhalation of arsenic-containing dusts represents a more direct exposure on the airways, and thus, the potential for similar or exacerbated lung dysfunction, the consequences of such inhalation is not known.
The researchers are determining the impact of real world and synthetic arsenic-containing dust particulates on airway epithelial health and lung function. Their integrated approach uses high capacity in vitro toxicity evaluation to inform on dust particulates that will be used in well-established primary culture mechanistic in vitro and in vivo models of airway function. Their hypothesis is that arsenic exposure by inhalation leads to EMT that permanently reduces airway epithelial barrier function and increases the risk of airway/lung disease. These alterations are in part mediated through induction/modulation of NADPH oxidase (NOX) and dual oxidase (DUOX) activity leading to increased production of reactive oxygen species (ROS).
The researchers aim to:
- Use integrative, dissection, and synergistic approaches to determine mining-associated dust toxicity on airway epithelial cells.
- Determine if exposure of mining dusts results in airway EMT.
The team anticipates that successful completion of these studies will establish a mechanistic understanding of the contribution of arsenic (or other metals) in real world dusts (such as those found in mining communities) to lung disease.