Assessment of a 72-Hour Repeated Exposure to Swedish Snus Extract
Food and Chemical Toxicology 125 (2019) 252–270 Contents lists available at ScienceDirect Food and Chemical Toxicology journal homepage: www.elsevier.com/locate/foodchemtox Assessment of a 72-hour repeated exposure to Swedish snus extract and total T particulate matter from 3R4F cigarette smoke on gingival organotypic cultures ∗ Filippo Zanettia, , Alain Sewera, Bjoern Titza, Walter K. Schlageb, Anita R. Iskandara, Athanasios Kondylisa, Patrice Leroya, Emmanuel Guedja, Keyur Trivedia, Ashraf Elamina, Florian Martina, Stefan Frentzela, Nikolai V. Ivanova, Manuel C. Peitscha, Julia Hoenga a PMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchâtel, Switzerland b Biology Consultant, Max-Baermann-Str. 21, 51429 Bergisch Gladbach, Germany ARTICLE INFO ABSTRACT Keywords: Swedish snus is a smokeless tobacco product that contains reduced levels of harmful compounds compared with Cigarette smoke cigarette smoke. In Sweden, where snus use exceeds smoking among men, relatively low rates of major smoking- Oral health related diseases have been recorded. To better understand how snus use could align with current tobacco harm Swedish snus reduction strategies, its potential mechanisms of toxicity must be investigated. Systems toxicology This study aimed to determine, via a systems toxicology approach, the biological impact of repeated 72-hour Air-liquid interface exposure of human gingival epithelial organotypic cultures to extracts from both a commercial and a reference Smokeless tobacco product snus and the total particulate matter (TPM) from cigarette smoke. At concentrations relevant for human use, cultures treated with snus extracts induced mild, generally reversible biological changes, while TPM treatment induced substantial morphological and inflammatory alterations. Network enrichment analysis and integrative analysis of the global mRNA and miRNA expression profiles indicated a limited and mostly transient impact of the snus extracts, in particular on xenobiotic metabolism, while the effects of TPM were marked and sustained over time.
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