Abstract Wildfires are increasing at an alarming rate in the U.S. and globally. Numerous health effects are associated with exposure to wildfire particulate matter (PM) exposures, including an association with increased risk of cancer in wildland firefighters. However, more research is needed to understand the mechanisms driving these responses. Our hypothesis is that wood smoke particles (WSP) elicit events associated with premalignancy in human lung epithelial cells. For a wildfire PM surrogate, we used Douglas fir WSP generated by combustion with a custom-designed emission hood and tested the WSP on several critical cellular events, known to be hallmarks of cancer, using a bronchial epithelial cell line (BEAS-2B). Inflammatory mediators and dysregulation of gap junctional intercellular communication (GJIC) were evaluated as well as polycyclic aromatic hydrocarbons (PAHs) identified in WSP using gas chromatography-mass spectrometry (GC/MS). mRNA expression of the pro-tumorigenic markers TNF, IL-6, COX-2, IL-8 and EREG, as well as enzymes associated with PAH metabolism (CYP1A1 and CYP1B1) were significantly elevated in WSP-treated cells compared to controls. In addition, a marked decrease was observed in the expression of gap junction genes (GJA1 and GJB2) along with decreased activity of GJIC in response to WSP. Parthenolide, a pan-anti-inflammatory and anti-cancer compound, prevented WSP-induced dysregulation of GJIC and TNF mRNA expression. Lastly, validation of CYPs and IL6 responses were observed using primary human bronchial epithelial cells in air liquid interface (ALI) cultures. These foundational studies provide mechanistic insight into how wildfire smoke PM induces early premalignant events that need to be further investigated.
Bauer et al. (Thu,) studied this question.