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Combined Chronic Toxicity and Carcinogenicity of Aerosol from a Heated Tobacco Product (microRNA data).


ABSTRACT: Smoking cessation is the most effective measure for reducing the risk of smoking-related diseases but switching to less harmful products (modified-risk tobacco products) can be an alternative for smokers who would otherwise not quit. In an 18-month chronic carcinogenicity/toxicity study in A/J mice (OECD Test Guideline 453), we assessed the Tobacco Heating System 2.2 (THS 2.2), a candidate modified-risk tobacco product based on the heat-not-burn principle, compared with 3R4F cigarette smoke (CS). To capture toxicity- and disease-relevant mechanisms, we complemented standard toxicology endpoints with in-depth systems toxicology analyses. In this part of our publication series, we report on the integrative assessment of the apical and molecular exposure effects on the respiratory tract (nose, larynx, and lung). Across the respiratory tract, we found differences in the inflammatory response following 3R4F CS exposure (e.g., an antimicrobial peptide response in the nose), and both shared and distinct oxidative and xenobiotic responses. Compared with 3R4F CS, THS 2.2 aerosol exposure exerted far fewer effects on respiratory tract histology, including adaptive tissue changes in nasal and laryngeal epithelium and inflammation and emphysematous changes in the lung. Integrative analysis of the molecular alterations confirmed the substantially lower impact of THS 2.2 aerosol than 3R4F CS on toxicologically and disease-relevant molecular processes such as inflammation, oxidative stress responses, and activation of xenobiotic metabolism. In summary, this work exemplifies how apical and molecular endpoints can be combined effectively for toxicology assessment and further supports reduced respiratory health risks of THS 2.2 aerosol.

ORGANISM(S): Mus musculus

SUBMITTER: Karsta Luettich 

PROVIDER: E-MTAB-8541 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Reduced Chronic Toxicity and Carcinogenicity in A/J Mice in Response to Life-Time Exposure to Aerosol From a Heated Tobacco Product Compared With Cigarette Smoke.

Wong Ee Tsin ET   Luettich Karsta K   Krishnan Subash S   Wong Sin Kei SK   Lim Wei Ting WT   Yeo Demetrius D   Büttner Ansgar A   Leroy Patrice P   Vuillaume Grégory G   Boué Stéphanie S   Hoeng Julia J   Vanscheeuwijck Patrick P   Peitsch Manuel C MC  

Toxicological sciences : an official journal of the Society of Toxicology 20201101 1


We conducted an inhalation study, in accordance with Organisation for Economic Co-operation and Development Test Guideline 453, exposing A/J mice to tobacco heating system (THS) 2.2 aerosol or 3R4F reference cigarette smoke (CS) for up to 18 months to evaluate chronic toxicity and carcinogenicity. All exposed mice showed lower thymus and spleen weight, blood lymphocyte counts, and serum lipid concentrations than sham mice, most likely because of stress and/or nicotine effects. Unlike THS 2.2 aer  ...[more]

Publication: 1/2

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