In vitro RNA-seq-based toxicogenomics assessment shows reduced biological effect of tobacco heating products when compared to cigarette smoke

• Published in: Scientific reports Vol. 8; no. 1; pp. 1145 - 18
• Main Authors: Haswell, Linsey E., Corke, Sarah, Verrastro, Ivan, Baxter, Andrew, Banerjee, Anisha, Adamson, Jason, Jaunky, Tomasz, Proctor, Christopher, Gaça, Marianna, Minet, Emmanuel
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.02.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/21; 38/77; 38/91; 631/337/2019; 631/553; Aerosols; Aerosols - pharmacology; Cell Culture Techniques; Cellular stress response; Chronic obstructive pulmonary disease; Cigarette smoke; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Heating; Humanities and Social Sciences; Humans; Inflammation; multidisciplinary; Nicotiana - chemistry; Ontology; Respiratory Mucosa - cytology; Respiratory Mucosa - drug effects; Respiratory Mucosa - metabolism; Respiratory tract; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Sequence Analysis, RNA; Smoke - analysis; Tobacco; Tobacco Products - analysis; Toxicogenetics - methods; Transcriptome; Wounding; Xenobiotics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-19627-0

The battery of regulatory tests used to evaluate the risk of novel tobacco products such as heated tobacco products (THPs) presents some limitations including a bias towards the apical endpoint tested, and limited information on the mode of action. This is driving a paradigm shift to more holistic systems biology approaches. In this study, we used RNA-sequencing to compare the transcriptomic perturbations following acute exposure of a 3D airway tissue to the aerosols from two commercial THPs and a reference 3R4F cigarette. 2809 RNAs were differentially expressed for the 3R4F treatment and 115 and 2 RNAs for the two THPs (pFDR < 0.05, FC > 1.5), respectively. The relationship between the identified RNA features and gene ontologies were mapped showing a strong association with stress response, xenobiotics metabolism, and COPD-related terms for 3R4F. In contrast, fewer ontologies were found enriched for the THPs aerosols. “Response to wounding” was a common COPD-related term over-represented for the two THPs but at a reduced significance. Quantification of a cytokine panel post-exposure confirmed a pro-inflammatory effect of cigarette smoke but not for THPs. In conclusion, THPs have a reduced impact on gene expression compared to 3R4F.