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
Lantz and his research team are completing their first inhalation exposures to real world dusts that were collected from the mine tailings area at the Iron King Mine and Humboldt Smelter Superfund site by University of Arizona environmental researchers. Pregnant mice and their new borne pups were exposed to the dusts. Preliminary findings indicate that exposures to these dusts results in increased airway reactivity, similar to what they have seen following inhalation of synthetic arsenic-containing dusts. Analysis of the effects of inhalation of these real world dusts during sensitive developmental times is continuing. Their data have predicted that exposure to arsenic during early life can alter lung function. In collaboration with colleagues in Mexico, the research team has shown that following in utero and early life exposures, urinary arsenic levels are associated with decrements in lung function in children ages 6-12. Water levels of arsenic in this population are high. However, the children live in an arid, dusty environment where exposure may also be occurring from exposure to arsenic containing dusts. The relative contribution of these two routes of exposure in this population is not known. Pulmonary functional alterations are also associated with changes in matrixmetalloproteinase-9 and soluble receptor for advanced glycation end products, two biomarkers the team has previously identified as being altered in the lungs of adults exposed to arsenic. They have continued to investigate epithelial to mesenchymal transition (EMT) as a target pathway for arsenic induced changes in the lung phenotype. They have shown that arsenic exposures increase the expression of EMT genes and proteins in 12 day old pups. Some of these alterations continue into adulthood in the mice.
In complementary work, the researchers have improved their ability to measure in high-capacity system toxic and sub-cytotoxic cellular responses following exposure to environmental or industrial exposures using the xCELLigence real time cell analysis (RTCA) platform. They have published airway epithelial effects of arsenic, have in preparation the effects of nanoparticulates (hafnium oxides) and have gathered preliminary data on dust exposure from mining sites/control sites. The research team anticipates using this high capacity system to screen numerous dust samples to better define airway epithelial toxicity of various compounds.