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Respiratory Effects of Exposure to Aerosol From the Candidate Modified-Risk Tobacco Product THS 2.2 in an 18-Month Systems Toxicology Study With A/J Mice

Smoking cessation is the most effective measure for reducing the risk of smoking-related diseases. However, switching to less harmful products (modified-risk tobacco products [MRTP]) can be an alternative to help reduce the risk for adult smokers who would otherwise continue to smoke. In an 18-month...

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Autores principales: Titz, Bjoern, Sewer, Alain, Luettich, Karsta, Wong, Ee Tsin, Guedj, Emmanuel, Nury, Catherine, Schneider, Thomas, Xiang, Yang, Trivedi, Keyur, Vuillaume, Grégory, Leroy, Patrice, Büttner, Ansgar, Martin, Florian, Ivanov, Nikolai V, Vanscheeuwijck, Patrick, Hoeng, Julia, Peitsch, Manuel C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657339/
https://www.ncbi.nlm.nih.gov/pubmed/32780831
http://dx.doi.org/10.1093/toxsci/kfaa132
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author Titz, Bjoern
Sewer, Alain
Luettich, Karsta
Wong, Ee Tsin
Guedj, Emmanuel
Nury, Catherine
Schneider, Thomas
Xiang, Yang
Trivedi, Keyur
Vuillaume, Grégory
Leroy, Patrice
Büttner, Ansgar
Martin, Florian
Ivanov, Nikolai V
Vanscheeuwijck, Patrick
Hoeng, Julia
Peitsch, Manuel C
author_facet Titz, Bjoern
Sewer, Alain
Luettich, Karsta
Wong, Ee Tsin
Guedj, Emmanuel
Nury, Catherine
Schneider, Thomas
Xiang, Yang
Trivedi, Keyur
Vuillaume, Grégory
Leroy, Patrice
Büttner, Ansgar
Martin, Florian
Ivanov, Nikolai V
Vanscheeuwijck, Patrick
Hoeng, Julia
Peitsch, Manuel C
author_sort Titz, Bjoern
collection PubMed
description Smoking cessation is the most effective measure for reducing the risk of smoking-related diseases. However, switching to less harmful products (modified-risk tobacco products [MRTP]) can be an alternative to help reduce the risk for adult smokers who would otherwise continue to smoke. In an 18-month chronic carcinogenicity/toxicity study in A/J mice (OECD Test Guideline 453), we assessed the aerosol of Tobacco Heating System 2.2 (THS 2.2), a candidate MRTP 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 integrative assessment of the apical and molecular exposure effects on the respiratory tract (nose, larynx, and lungs). Across the respiratory tract, we found changes in inflammatory response following 3R4F CS exposure (eg, antimicrobial peptide response in the nose), with both shared and distinct oxidative and xenobiotic responses. Compared with 3R4F CS, THS 2.2 aerosol exerted far fewer effects on respiratory tract histology, including adaptive tissue changes in nasal and laryngeal epithelium and inflammation and emphysematous changes in the lungs. Integrative analysis of molecular changes 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 xenobiotic metabolism. In summary, this work exemplifies how apical and molecular endpoints can be combined effectively for toxicology assessment and further supports findings on the reduced respiratory health risks of THS 2.2 aerosol.
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spelling pubmed-76573392020-11-17 Respiratory Effects of Exposure to Aerosol From the Candidate Modified-Risk Tobacco Product THS 2.2 in an 18-Month Systems Toxicology Study With A/J Mice Titz, Bjoern Sewer, Alain Luettich, Karsta Wong, Ee Tsin Guedj, Emmanuel Nury, Catherine Schneider, Thomas Xiang, Yang Trivedi, Keyur Vuillaume, Grégory Leroy, Patrice Büttner, Ansgar Martin, Florian Ivanov, Nikolai V Vanscheeuwijck, Patrick Hoeng, Julia Peitsch, Manuel C Toxicol Sci Molecular, Biochemical, and Systems Toxicology Smoking cessation is the most effective measure for reducing the risk of smoking-related diseases. However, switching to less harmful products (modified-risk tobacco products [MRTP]) can be an alternative to help reduce the risk for adult smokers who would otherwise continue to smoke. In an 18-month chronic carcinogenicity/toxicity study in A/J mice (OECD Test Guideline 453), we assessed the aerosol of Tobacco Heating System 2.2 (THS 2.2), a candidate MRTP 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 integrative assessment of the apical and molecular exposure effects on the respiratory tract (nose, larynx, and lungs). Across the respiratory tract, we found changes in inflammatory response following 3R4F CS exposure (eg, antimicrobial peptide response in the nose), with both shared and distinct oxidative and xenobiotic responses. Compared with 3R4F CS, THS 2.2 aerosol exerted far fewer effects on respiratory tract histology, including adaptive tissue changes in nasal and laryngeal epithelium and inflammation and emphysematous changes in the lungs. Integrative analysis of molecular changes 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 xenobiotic metabolism. In summary, this work exemplifies how apical and molecular endpoints can be combined effectively for toxicology assessment and further supports findings on the reduced respiratory health risks of THS 2.2 aerosol. Oxford University Press 2020-08-11 /pmc/articles/PMC7657339/ /pubmed/32780831 http://dx.doi.org/10.1093/toxsci/kfaa132 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of the American Medical Informatics Association. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Molecular, Biochemical, and Systems Toxicology
Titz, Bjoern
Sewer, Alain
Luettich, Karsta
Wong, Ee Tsin
Guedj, Emmanuel
Nury, Catherine
Schneider, Thomas
Xiang, Yang
Trivedi, Keyur
Vuillaume, Grégory
Leroy, Patrice
Büttner, Ansgar
Martin, Florian
Ivanov, Nikolai V
Vanscheeuwijck, Patrick
Hoeng, Julia
Peitsch, Manuel C
Respiratory Effects of Exposure to Aerosol From the Candidate Modified-Risk Tobacco Product THS 2.2 in an 18-Month Systems Toxicology Study With A/J Mice
title Respiratory Effects of Exposure to Aerosol From the Candidate Modified-Risk Tobacco Product THS 2.2 in an 18-Month Systems Toxicology Study With A/J Mice
title_full Respiratory Effects of Exposure to Aerosol From the Candidate Modified-Risk Tobacco Product THS 2.2 in an 18-Month Systems Toxicology Study With A/J Mice
title_fullStr Respiratory Effects of Exposure to Aerosol From the Candidate Modified-Risk Tobacco Product THS 2.2 in an 18-Month Systems Toxicology Study With A/J Mice
title_full_unstemmed Respiratory Effects of Exposure to Aerosol From the Candidate Modified-Risk Tobacco Product THS 2.2 in an 18-Month Systems Toxicology Study With A/J Mice
title_short Respiratory Effects of Exposure to Aerosol From the Candidate Modified-Risk Tobacco Product THS 2.2 in an 18-Month Systems Toxicology Study With A/J Mice
title_sort respiratory effects of exposure to aerosol from the candidate modified-risk tobacco product ths 2.2 in an 18-month systems toxicology study with a/j mice
topic Molecular, Biochemical, and Systems Toxicology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657339/
https://www.ncbi.nlm.nih.gov/pubmed/32780831
http://dx.doi.org/10.1093/toxsci/kfaa132
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