Molecular biomarkers associated with environmental naphthalene exposure in the respiratory system

Naphthalene (NPT) is a polycyclic aromatic hydrocarbon (PAH) contaminant found in tobacco smoke and various consumer products, causing widespread toxic exposure to human. NPT-induced cell toxicity depends on a metabolic activation step mediated by cytochrome P450 (CYP) and primarily affects non-ciliated club cells of the conducting airways. Here, we characterize the histological features and gene expression profiles of airway epithelial cells following NPT-induced injury and identify early response genes (ERGs) that are sensitive to NPT in respiratory organs. NPT results in the detachment and sloughing of pseudostratified airway epithelial cells within 24 h post-injection (hpi). From bulk transcriptomic analyses of NPT-treated mouse lungs, we observed significant upregulation of genes associated with responses to external stimuli and chemical exposure at 24 hpi. To identify novel molecular biomarkers of chemical injury, we selected 11 candidate genes functionally related to these processes for further investigation. Most of these genes are upregulated in cells isolated from bronchoalveolar lavage fluid (BALF) of NPT-injured lungs. Moreover, the selected ERGs are dynamically upregulated in a cell type-specific manner in the trachea and lung following NPT injury, with Vimentin and E-Cadherin marking mesenchymal and epithelial cell responses to NPT, respectively. Taken together, our findings reveal that NPT induces cytotoxicity and impairs cell adhesion in airway epithelial cells. From respiratory tissues, BALF cells, and a human airway epithelial cell line, we identify ERGs that serve as potential molecular biomarkers of respiratory exposure to environmental toxicants.