Superfund Research Program
Role of NRF2 in the Pulmonary Response to Inhaled Mine Tailing Dust
Project Leader: Donna D. Zhang
Co-Investigators: Scott Boitano, Robert Clark Lantz
Grant Number: P42ES004940
Funding Period: 2017-2020
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Final Progress Reports
Year: 2019
An increasing body of literature indicates that chronic exposure to arsenic is linked to increased risk of developing certain diseases, including lung cancer. Even though the adverse health effects associated with arsenic exposure are known, the mechanisms underlying prolonged exposure to arsenic that drive lung cancer initiation and progression have not been fully elucidated. The research team’s studies were among the first to identify that exposure to arsenic activates the Nrf2 pathway. One interesting finding from this work is that short-term activation of Nrf2 is generally protective, whereas chronic activation can lead to numerous deleterious effects, including protecting cancer cells from establish cancer treatments. As such, this project aims to determine how chronic activation of Nrf2, via repeated exposure to arsenic-containing dust particles, enhances lung tumor formation and progression, including whether or not activation of this pathway prior to exposure can lessen or prevent tumor formation. Over the past year, the research team: (1) has identified a number of biomarkers associated with chronic arsenic exposure; (2) is in the process of finalizing and analyzing tissue samples from mice exposed to arsenic-containing dust to determine what pathways downstream of Nrf2 are activated during exposure, as well as if pretreatment with an Nrf2 inducer ameliorates the pro-tumorigenic changes caused by arsenic; and (3) is building the foundation for the research team’s new projects investigating arsenic promotion of type II diabetes. The past year has increased the research team’s understanding of how arsenic-induced activation of Nrf2 promotes lung cancer, and whether therapeutic activation of Nrf2 prior to exposure can benefit exposed populations.