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COMPARATIVE SYSTEMS TOXICOLOGY ANALYSIS OF CIGARETTE SMOKE AND AEROSOL FROM A CANDIDATE MODIFIED RISK TOBACCO PRODUCT IN ORGANOTYPIC HUMAN GINGIVAL EPITHELIAL CULTURES: A 3-DAY REPEATED EXPOSURE STUDY.


ABSTRACT: Smoking is one of the major lifestyle-related risk factors for periodontal diseases. Modified risk tobacco products (MRTP) offer a promising alternative in the harm reduction strategy for adult smokers unable to quit. Using a systems toxicology approach, we investigated and compared the exposure effects of a reference cigarette (3R4F) and a heat-not-burn technology-based candidate MRTP, the Tobacco Heating System (THS) 2.2. Human gingival epithelial organotypic cultures were repeatedly exposed (3 days) for 28 min at two matching concentrations of cigarette smoke (CS) or THS2.2 aerosol. Results showed only minor histopathological alterations and minimal cytotoxicity upon THS2.2 aerosol exposure compared to CS (1% for THS2.2 aerosol vs. 30% for CS, at the high concentration). Among the 14 proinflammatory mediators analyzed, only 5 exhibited significant alterations with THS2.2 exposure compared with 11 upon CS exposure. Transcriptomic and metabolomic analysis indicated a general reduction of the impact in THS2.2 aerosol-exposed samples with respect to CS (∼79% lower biological impact for the high THS2.2 aerosol concentration compared to CS, and 13 metabolites significantly perturbed for THS2.2 vs. 181 for CS). This study indicates that exposure to THS2.2 aerosol had a lower impact on the pathophysiology of human gingival organotypic cultures than CS.

ORGANISM(S): Homo sapiens

SUBMITTER: Filippo Zanetti 

PROVIDER: E-MTAB-5608 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Comparative systems toxicology analysis of cigarette smoke and aerosol from a candidate modified risk tobacco product in organotypic human gingival epithelial cultures: A 3-day repeated exposure study.

Zanetti Filippo F   Titz Bjoern B   Sewer Alain A   Lo Sasso Giuseppe G   Scotti Elena E   Schlage Walter K WK   Mathis Carole C   Leroy Patrice P   Majeed Shoaib S   Torres Laura Ortega LO   Keppler Brian R BR   Elamin Ashraf A   Trivedi Keyur K   Guedj Emmanuel E   Martin Florian F   Frentzel Stefan S   Ivanov Nikolai V NV   Peitsch Manuel C MC   Hoeng Julia J  

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 20161223


Smoking is one of the major lifestyle-related risk factors for periodontal diseases. Modified risk tobacco products (MRTP) offer a promising alternative in the harm reduction strategy for adult smokers unable to quit. Using a systems toxicology approach, we investigated and compared the exposure effects of a reference cigarette (3R4F) and a heat-not-burn technology-based candidate MRTP, the Tobacco Heating System (THS) 2.2. Human gingival epithelial organotypic cultures were repeatedly exposed (  ...[more]

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