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Updated: Jun 5, 2026

Impact Assessment of Repeated Exposure of Organotypic 3D Bronchial and Nasal Tissue Culture Models to Whole Cigarette Smoke
Published on: February 12, 2015
Nicotine metabolite ratio predicts smoking topography and carcinogen biomarker level
Andrew A Strasser1, Neal L Benowitz, Angela G Pinto
1Department of Psychiatry and Abramson Cancer Center, University of Pennsylvania, 3535 Market Street, Suite 4100, Philadelphia, PA 19104-3309, USA. strasse3@mail.med.upenn.edu
Background:
Variability in smoking behavior is partly attributable to heritable individual differences in nicotine clearance rates. This can be assessed as the ratio of the metabolites cotinine and 3'-hydroxycotinine (referred to as the nicotine metabolism ratio; NMR). We hypothesized that faster NMR would be associated with greater cigarette puff volume and higher levels of total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a carcinogen biomarker.
Methods:
Current smokers (n = 109) smoked one of their preferred brand cigarettes through a smoking topography device and provided specimens for NMR and total NNAL assays.
Results:
Faster nicotine metabolizers (third and fourth quartiles versus first quartile) based on the NMR exhibited significantly greater total puff volume and total NNAL; the total puff volume by daily cigarette consumption interaction was a significant predictor of total NNAL level.
Conclusion:
A heritable biomarker of nicotine clearance predicts total cigarette puff volume and total NNAL.
Impact:
If validated, the NMR could contribute to smoking risk assessment in epidemiologic studies and potentially in clinical practice.
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