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
Final Progress Reports
The Toxicological Impact of Mine Tailings Dust on Lung Epithelial Barrier Function Project has focused on the effects of inhalation exposure to real world dusts containing arsenic and other metals. The research team have developed a mouse model system that allows for evaluation of airway toxicity and specifically the lung structure and function. Using unique early life exposures in this model system, the research team have shown that: (1) the most significant changes in lung structure and function were observed in male mice when exposure occurred continuously throughout development (both in utero and post-natally) (Witten et al., 2019) These changes include increased airway hyper-reactivity, increased expression of proteins that indicate changes in the lung epithelial cell lining, and increased expression of inflammatory proteins; (2) in utero exposures through maternal inhalation can make the lung of male mice more susceptible to severe responses to subsequent postnatal exposures. This may be due to alterations in gene regulation, immune response, molecular signaling, and growth factors involved in lung development. Given these results, the research team used cultured airway epithelial cells to show that arsenic inhibits the formation of a tight barrier between the apical and basal sides of the cells. The inability to form a tight barrier can lead to the inflammation and airway hyper-reactivity that the research team have seen in their animal models; (3) a specific lung anti-inflammatory protein, club cell 16 (CC16), that has been implicated as an indicator of loss of lung function has a significant decrease in expression when mice are developmentally exposed to real world dust from the Iron King Mine and Humboldt Smelter Superfund site.