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Drug Dependence Clinical Research Program: New Biomarkers for Tobacco Exposure

Principal Investigator: Reese Jones

Funding Mechanism:  Intra-Departmental Delegation of Authority (IDDA)

ID Number: 3P30DA012393-14S1

Award Date:  1/22/2014

Institution:  University of California-San Francisco 

While data are available on the chemical composition of, and human exposure to, tobacco toxicants in cigarettes, much less is known about new and emerging tobacco products such as snus, electronic cigarettes, and hookah (waterpipe).  The goal of this study is to develop two new biomarkers of exposure: the tobacco alkaloid nicotelline as a biomarker for tobacco smoke particulate matter (TPM, or "tar"), and pseudooxynicotine (PON), the chemical precursor to the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). To develop these biomarkers, researchers will analyze urine samples from 120 subjects aged 18-70 using hookah (waterpipe), snus, electronic cigarettes, cigarettes, cigars, or oral snuff. Researchers will also analyze these tobacco products for toxic substances and their precursors. Specific aims are: (1) to explore the utility of nicotelline as a biomarker for the particle phase of tobacco smoke by characterizing levels in smokers' urine and correlating these levels with existing measures of smoke exposure, including cigarettes per day, amount of tobacco burned, and established biomarkers such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and polycyclic aromatic hydrocarbons (PAH); (2) to evaluate PON and its metabolites as biomarkers of exposure to NNK and other tobacco-specific nitrosamines by developing analytical methods for determining urine concentrations of PON and likely metabolites; and (3) to measure concentrations of PON, NNK, other alkaloids, and toxic substances in new and emerging tobacco products in order to determine whether concentrations in the products correlate with urine biomarker concentrations. These new biomarkers will advance the field of tobacco exposure assessment and may inform future regulatory activities.

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