The Tobacco Constituent and Biomarker Assessment Core will provide a unique resource for Projects 1, 2 and 4. Investigators in this Core comprise one of the leading academic laboratories in the world for chemical analysis of tobacco constituents and related metabolites and biomarkers. For Project 1, the Core will quantify several important constituents of tobacco, namely tobacco alkaloids, (3-carbolines, and acetaldehyde and their biomarkers. For Projects 2 and 4, the Core will quantify certain important urinary metabolites of tobacco and tobacco smoke constituents as well as urinary metabolites related to inflammation and oxidative damage. The following urinary metabolites will be quantified: nicotine equivalents (the total of nicotine, cotinine, and trans-3'-hydroxycotinine and their glucuronides), total NNAL (the total of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides), total NNN (the total of free and glucuronidated N'-nitrosonornicotine), mercapturic acids of the volatile carcinogens 1,3-butadiene, benzene, acrolein, crotonaldehyde, and ethylene oxide, and the inflammation and oxidative damage biomarkers 11-a-hydroxy-9,15-dioxo-2,3,4,5-tetranorprostane-1,20-dioic acid (PGE-M) and 9,11,15-trihydroxyprosta-5,13-dien-1-oic acid. We will also quantify the formaldehyde-DNA adduct, N6-hydroxymethyldeoxyadenosine in leukocyte DNA, for Project 4. These biomarkers will provide crucial information for the research being carried out in Projects 1, 2 and 4.
Methods for achieving reduction in public health harm from use of tobacco products are critical for decreasing the human cancer toll of tobacco use. The biomarkers being quantified in this core are representative of many of the major carcinogenic and tumor enhancing constituents known to be present in tobacco products. Quantifying these biomarkers will provide an important tool for the evaluation of tobacco products to determine their potential impact on public health.
|Bickel, Warren K; Johnson, Matthew W; Koffarnus, Mikhail N et al. (2014) The behavioral economics of substance use disorders: reinforcement pathologies and their repair. Annu Rev Clin Psychol 10:641-77|
|Ho, Yen-Yi; Baechler, Emily C; Ortmann, Ward et al. (2014) Using gene expression to improve the power of genome-wide association analysis. Hum Hered 78:94-103|
|Vogel, Rachel Isaksson; Hertsgaard, Louise A; Dermody, Sarah S et al. (2014) Sex differences in response to reduced nicotine content cigarettes. Addict Behav 39:1197-204|
|Bickel, Warren K; Koffarnus, Mikhail N; Moody, Lara et al. (2014) The behavioral- and neuro-economic process of temporal discounting: A candidate behavioral marker of addiction. Neuropharmacology 76 Pt B:518-27|