Peer-Reviewed 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, F.; Titz, B.; Sewer, A.; Lo Sasso, G.; Scotti, E.; Schlage, W. K.; Mathis, C.; Leroy, P.; Majeed, S.; Ortega Torres, L. ; Keppler, B. R.; Elamin, A.; Trivedi, K.; Guedj, E.; Martin, F.; Frentzel, S.; Ivanov, N. V.; Peitsch, M. C.; Hoeng, J.

      Published
      Dec 23, 2016
      DOI
      10.1016/j.fct.2016.12.027
      PMID
      28025120
      Link to publication
      Topic
      Summary

      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 ( approximately 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.

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      Reduced Risk Products ("RRPs”) is the term we use to refer to products that present, are likely to present, or have the potential to present less risk of harm to smokers who switch to these products versus continuing smoking. PMI has a range of RRPs in various stages of development, scientific assessment and commercialization. All of our RRPs are smoke-free products that deliver nicotine with far lower quantities of harmful and potentially harmful constituents than found in cigarette smoke.