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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
1P01CA138338-01A1
Application #
7786644
Study Section
Special Emphasis Panel (ZCA1-RPRB-7 (O1))
Project Start
2009-12-01
Project End
2014-11-30
Budget Start
2009-12-01
Budget End
2011-03-31
Support Year
1
Fiscal Year
2010
Total Cost
$161,601
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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
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
Hecht, Stephen S (2017) Oral Cell DNA Adducts as Potential Biomarkers for Lung Cancer Susceptibility in Cigarette Smokers. Chem Res Toxicol 30:367-375
Patel, Yesha M; Park, Sunghim L; Han, Younghun et al. (2016) Novel Association of Genetic Markers Affecting CYP2A6 Activity and Lung Cancer Risk. Cancer Res 76:5768-5776
Ma, Bin; Ruszczak, Chris; Jain, Vipin et al. (2016) Optimized Liquid Chromatography Nanoelectrospray-High-Resolution Tandem Mass Spectrometry Method for the Analysis of 4-Hydroxy-1-(3-pyridyl)-1-butanone-Releasing DNA Adducts in Human Oral Cells. Chem Res Toxicol 29:1849-1856
Patel, Yesha M; Park, Sungshim L; Carmella, Steven G et al. (2016) Metabolites of the Polycyclic Aromatic Hydrocarbon Phenanthrene in the Urine of Cigarette Smokers from Five Ethnic Groups with Differing Risks for Lung Cancer. PLoS One 11:e0156203
Zanetti, Krista A; Wang, Zhaoming; Aldrich, Melinda et al. (2016) Genome-wide association study confirms lung cancer susceptibility loci on chromosomes 5p15 and 15q25 in an African-American population. Lung Cancer 98:33-42

Showing the most recent 10 out of 40 publications