Advanced in vitro exposure systems.

Systems toxicology assessment of repeated exposure to cigarette smoke and a candidate modified-risk tobacco product aerosol on gingival organotypic cultures

10. Sep. 2017

Eurotox 2017

Filippo Zanetti, Alain Sewer, Patrice Leroy, Shoaib Majeed, Laura Ortega Torres, Céline Merg, Maica Corciulo, Keyur Trivedi, Emmanuel Guedj, Ashraf Elamin, Stefan Frentzel, Nikolai V. Ivanov, Manuel C. Peitsch, Julia Hoeng
Philip Morris International Research and Development, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland

The objective of this study was to assess and compare the effects of repeated exposures to the aerosol of CHTP1.2 with cigarette smoke generated from reference cigarettes (3R4F) on human gingival organotypic epithelial cultures. The results were evaluated in using Adenylate Kinase (AK)-based cytotoxicity assay, histological analysis, pro-inflammatory mediators and Microarray data processing and analysis.

The poster was presented at Eurotox 2017, http://www.eurotox2017.com

Introduction. Cigarette smoke (CS) has been reported to increase predisposition to oral cancer and recognized as a risk factor for many conditions including periodontal diseases, gingivitis and benign mucosal disorders [1]. Tobacco harm reduction through the development of Modified Risk Tobacco Products (MRTP) provides a promising opportunity for adult smokers, who would otherwise continue cigarette smoking. MRTPs are defined by the US FDA as "any tobacco product that is sold or distributed for use to reduce harm or the risk of tobacco-related disease associated with commercially marketed tobacco products"[2]. A candidate MRTP, the Carbon Heated Tobacco Product (CHTP)1.2, is a novel patented tobacco product, which uses a carbon source to heat a tobacco plug in a specially-designed stick to produce an aerosol which contains nicotine and tobacco flavor.

Objective. The objective of this study was to assess and compare the effects of repeated exposures (28- min daily for 3 days) to the aerosol of CHTP1.2 with CS generated from reference cigarettes (3R4F) on human gingival organotypic epithelial cultures. We employed a systems toxicology approach based on the measurement of cytotoxicity, histopathological modifications, proinflammatory mediator secretion and the modelling of computational network biology to investigate the impact of exposure on the gingival epithelial transcriptome.

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