Repeated Exposure to Eucalyptus Smoke Alters Pulmonary Gene Expression in Male Long-Evans Rats
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The expected increase in the frequency and intensity of wildland fires has led to concern for respiratory health in both occupational and public health settings. Hence, the purpose of this study was to assess alterations in the lung transcriptome following exposure to laboratory-generated wildland fire smoke. Male 12-week-old Long-Evans rats were exposed to either filtered air or smoke from eucalyptus biomass under smoldering conditions at a concentration of 11 ± 1.89 mg/m3 (low) or 23.7 ± 0.77 mg/m3 (high) for 1 hr/day over 2 weeks. Lungs were assessed for alterations in gene expression using RNA-seq (n=7-8/group). Differentially expressed genes (DEGs) were determined by Storey q-value ≤ 0.05 and analyzed by Ingenuity Pathway Analysis. Results revealed no DEGs in the low exposure concentration compared to filtered air. Conversely, the high exposure concentration resulted in 3,125 DEGs out of 13,879 genes assessed compared to filtered air, with 1,712 upregulated DEGs and 1,413 downregulated DEGs. The most significant Canonical Pathways from Core Analysis for the high exposure concentration predicted increased EIF2 Signaling and Signaling by Rho Family GTPases. Additionally, there were reductions in the Regulation of eIF4 and p7056K Signaling, and mTOR Signaling. The most significant Diseases and Biofunctions included nonhematologic malignant neoplasm and other non-descriptive cancer annotations. Our data suggest that short-term, episodic exposure to eucalyptus smoke results in robust changes to the lung transcriptome, providing insight into altered gene pathways that support the association between wildland fire smoke exposure and adverse respiratory outcomes. This abstract does not reflect U.S. EPA policy.