Network-based toxicogenomic approach to explore oral benzo(a)pyrene exposure effect on respiratory system

Abstract

Background Benzo(a)pyrene is known as a ubiquitous environmental pollutant. The general population can be exposed to benzo(a)pyrene through ambient air, tobacco smoke, water, and food. Genotoxicity and carcinogenicity are well-known adverse effects of benzo(a)pyrene exposure. However, few studies have focused on the effects of oral benzo(a)pyrene exposure on the respiratory system in terms of gene expression profiling. Objectives We explored the effect of benzo(a)pyrene on respiratory organs through bioinformatics analysis using public gene expression data. Key genes associated with respiratory toxicity were selected through network analysis and validated by Western blot and qRT-PCR. Results NRF2-mediated oxidative stress response and CREB signaling in neurons were identified as the main canonical pathways related to benzo(a)pyrene toxicity in the respiratory system. Potential biomarkers were validated in human lung cells. Conclusion Our study suggested canonical pathways related to benzo(a)pyrene toxicity in the respiratory system and validated potential biomarkers in human lung cells.