The Tobacco Smoke Constituent Biomarker Core will quantify urinary biomarkers of exposure to and metabolism of tobacco smoke toxicants and carcinogens. Total nicotine equivalents in urine will be quantified by measuring nicotine and its metabolites nicotine-/V-glucuronide, cotinine, cotinlne-/V-glucuronide, and trans-3'-hydroxycotinine and its glucuronides. Exposure to the tobacco-specific lung carcinogen 4- (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) will be assessed by quantitation of its urinary metabolites 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its N- and O-glucuronides. Exposure to and metabolism ofthe representative polycyclic aromatic hydrocarbon phenanthrene will be measured by quantifying Its metabolites f-1,/-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene and phenanthrols. Exposure to the volatile organic compounds benzene, acrolein, crotonaldehyde, and ethylene oxide will be measured by quantitation ofthe urinary mercapturic acids S-phenylmercapturic acid, 3- hydroxypropylmercapturic acid, 4-hydroxybut-2-ylmercapturic acid, and 2-hydroxyethymercapturic acid, respectively. The measurements will be carried out on a total of 2450 urine samples, and the results will be used by all projects. All assays use mass spectrometry with appropriately labeled internal standards for detection and quantitation, and all have been analytically validated with respect to accuracy and precision. Personnel in this Core have years of experience in the quantitation of urinary metabolites of tobacco smoke constituents and were the first to develop many of the methods being used. This Core is critical for the proposed studies in the program project relating metabolic phenotypes, as measured here, to the results of genome wide association studies and for determining differences in mechanisms of tobacco carcinogenesis in ethnic groups at different risk for lung cancer.

Public Health Relevance

Lung cancer is the leading cause of cancer death in the world and 90% of this toll is caused by cigarette smoking. The success of this program project depends on the analysis of tobacco constituent biomarkers in the urine of individuals from different ethnic groups, as proposed in this core. If the research supported by this core is successful, new insights will be gained for the prevention of lung cancer, which kills 3500 people every day.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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Special Emphasis Panel (ZCA1-RPRB-7)
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University of Minnesota Twin Cities
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Murphy, Sharon E; von Weymarn, Linda B; Parenteau, Marc et al. (2018) Influence of UGT2B10 Genotype on Urinary Excretion of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol- N-glucuronide by African American Smokers. Chem Res Toxicol 31:168-175
Degner, Amanda; Carlsson, Henrik; Karlsson, Isabella et al. (2018) Discovery of Novel N-(4-Hydroxybenzyl)valine Hemoglobin Adducts in Human Blood. Chem Res Toxicol :
Park, Sungshim L; Patel, Yesha M; Loo, Lenora W M et al. (2018) Association of internal smoking dose with blood DNA methylation in three racial/ethnic populations. Clin Epigenetics 10:110
Murphy, Sharon E; Park, Sungshim Lani; Balbo, Silvia et al. (2018) Tobacco biomarkers and genetic/epigenetic analysis to investigate ethnic/racial differences in lung cancer risk among smokers. NPJ Precis Oncol 2:17
Chai, Weiwen; Morimoto, Yukiko; Cooney, Robert V et al. (2017) Dietary Red and Processed Meat Intake and Markers of Adiposity and Inflammation: The Multiethnic Cohort Study. J Am Coll Nutr 36:378-385
Park, Sungshim L; Murphy, Sharon E; Wilkens, Lynne R et al. (2017) Association of CYP2A6 activity with lung cancer incidence in smokers: The multiethnic cohort study. PLoS One 12:e0178435
Murphy, Sharon E (2017) Nicotine Metabolism and Smoking: Ethnic Differences in the Role of P450 2A6. Chem Res Toxicol 30:410-419
Boldry, Emily J; Patel, Yesha M; Kotapati, Srikanth et al. (2017) Genetic Determinants of 1,3-Butadiene Metabolism and Detoxification in Three Populations of Smokers with Different Risks of Lung Cancer. Cancer Epidemiol Biomarkers Prev 26:1034-1042
Sangaraju, Dewakar; Boldry, Emily J; Patel, Yesha M et al. (2017) Isotope Dilution nanoLC/ESI+-HRMS3 Quantitation of Urinary N7-(1-Hydroxy-3-buten-2-yl) Guanine Adducts in Humans and Their Use as Biomarkers of Exposure to 1,3-Butadiene. Chem Res Toxicol 30:678-688
Peterson, Lisa A (2017) Context Matters: Contribution of Specific DNA Adducts to the Genotoxic Properties of the Tobacco-Specific Nitrosamine NNK. Chem Res Toxicol 30:420-433

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