Biological impact of cigarette smoke compared to an aerosol produced from a prototypic modified risk tobacco product on normal human bronchial epithelial cells.
Cigarette smoking causes serious and fatal diseases. The best way for smokers to avoid health risks is to quit smoking. Using modified risk tobacco products (MRTPs) may be an alternative to reduce the harm caused for those who are unwilling to quit smoking, but little is known about the toxic effects of MRTPs, nor were the molecular mechanisms of toxicity investigated in detail. The toxicity of an MRTP and the potential molecular mechanisms involved were investigated in high-content screening tests and whole genome transcriptomics analyses using human bronchial epithelial cells. The prototypic (p)MRTP that was tested had less impact than reference cigarette 3R4F on the cellular oxidative stress response and cell death pathways. Higher pMRTP aerosol extract concentrations had impact on pathways associated with the detoxification of xenobiotics and the reduction of oxidative damage. A pMRTP aerosol concentration up to 18 times higher than the 3R4F caused similar perturbation effects in biological networks and led to the perturbation of networks related to cell stress, and proliferation biology. These results may further facilitate the development of a systems toxicology-based impact assessment for use in future risk assessments in line with the 21st century toxicology paradigm, as shown here for an MRTP.
Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: ulrike.kogel@pmi.com.
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Kogel
Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: ignacio.gonzalezSuarez@pmi.com.
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Gonzalez Suarez
Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: yang.xiang@pmi.com.
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Xiang
Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: eric.dossin@pmi.com.
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Dossin
Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: philippealexandre.guy@pmi.com.
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Guy
Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: carole.mathis@pmi.com.
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Mathis
Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: diego.marescotti@pmi.com.
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Marescotti
Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: didier.goedertier@pmi.com.
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Goedertier
Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: florian.martin@pmi.com.
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Martin
Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: manuel.peitsch@pmi.com.
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Peitsch
Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: julia.hoeng@pmi.com.
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Hoeng
D000336:Aerosols / Q000009:adverse effects*; D001980:Bronchi; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019295:Computational Biology; D004847:Epithelial Cells / Q000187:drug effects*; D005786:Gene Expression Regulation; D006801:Humans; D020545:Respiratory Mucosa / Q000166:cytology*; D012906:Smoke / Q000009:adverse effects*; D062789:Tobacco Products / Q000009:adverse effects*; D059467:Transcriptome
D000336:Aerosols; D012906:Smoke
MRTP; Systems toxicology; in vitro