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.
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.
|Patel, Yesha M; Stram, Daniel O; Wilkens, Lynne R et al. (2015) The contribution of common genetic variation to nicotine and cotinine glucuronidation in multiple ethnic/racial populations. Cancer Epidemiol Biomarkers Prev 24:119-27|
|Zarth, Adam T; Carmella, Steven G; Le, Chap T et al. (2014) Effect of cigarette smoking on urinary 2-hydroxypropylmercapturic acid, a metabolite of propylene oxide. J Chromatogr B Analyt Technol Biomed Life Sci 953-954:126-31|
|Kotapati, Srikanth; Sangaraju, Dewakar; Esades, Amanda et al. (2014) Bis-butanediol-mercapturic acid (bis-BDMA) as a urinary biomarker of metabolic activation of butadiene to its ultimate carcinogenic species. Carcinogenesis 35:1371-8|
|Park, Sungshim Lani; Kotapati, Srikanth; Wilkens, Lynne R et al. (2014) 1,3-Butadiene exposure and metabolism among Japanese American, Native Hawaiian, and White smokers. Cancer Epidemiol Biomarkers Prev 23:2240-9|
|Jing, Meng; Wang, Yaohua; Upadhyaya, Pramod et al. (2014) Liquid chromatography-electrospray ionization-tandem mass spectrometry quantitation of urinary [pyridine-D4]4-hydroxy-4-(3-pyridyl)butanoic acid, a biomarker of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone metabolic activation in smokers. Chem Res Toxicol 27:1547-55|
|Murphy, Sharon E; Park, Sung-Shim L; Thompson, Elizabeth F et al. (2014) Nicotine N-glucuronidation relative to N-oxidation and C-oxidation and UGT2B10 genotype in five ethnic/racial groups. Carcinogenesis 35:2526-33|
|Sangaraju, Dewakar; Villalta, Peter W; Wickramaratne, Susith et al. (2014) NanoLC/ESI+ HRMS3 quantitation of DNA adducts induced by 1,3-butadiene. J Am Soc Mass Spectrom 25:1124-35|
|Narayanapillai, Sreekanth C; Balbo, Silvia; Leitzman, Pablo et al. (2014) Dihydromethysticin from kava blocks tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis and differentially reduces DNA damage in A/J mice. Carcinogenesis 35:2365-72|
|Zhang, Jianqi; Stram, Daniel O (2014) The role of local ancestry adjustment in association studies using admixed populations. Genet Epidemiol 38:502-15|
|Carmella, Steven G; Ming, Xun; Olvera, Natalie et al. (2013) High throughput liquid and gas chromatography-tandem mass spectrometry assays for tobacco-specific nitrosamine and polycyclic aromatic hydrocarbon metabolites associated with lung cancer in smokers. Chem Res Toxicol 26:1209-17|
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