Journal Article

Human urinary carcinogen metabolites: biomarkers for investigating tobacco and cancer

Stephen S. Hecht

in Carcinogenesis

Volume 23, issue 6, pages 907-922
Published in print June 2002 | ISSN: 0143-3334
Published online June 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.6.907
Human urinary carcinogen metabolites: biomarkers for investigating tobacco and cancer

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Measurement of human urinary carcinogen metabolites is a practical approach for obtaining important information about tobacco and cancer. This review presents currently available methods and evaluates their utility. Carcinogens and their metabolites and related compounds that have been quantified in the urine of smokers or non-smokers exposed to environmental tobacco smoke (ETS) include trans,trans-muconic acid (tt-MA) and S-phenylmercapturic acid (metabolites of benzene), 1- and 2-naphthol, hydroxyphenanthrenes and phenanthrene dihydrodiols, 1-hydroxypyrene (1-HOP), metabolites of benzo[a]pyrene, aromatic amines and heterocyclic aromatic amines, N-nitrosoproline, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides (NNAL and NNAL-Gluc), 8-oxodeoxyguanosine, thioethers, mercapturic acids, and alkyladenines. Nitrosamines and their metabolites have also been quantified in the urine of smokeless tobacco users. The utility of these assays to provide information about carcinogen dose, delineation of exposed vs. non-exposed individuals, and carcinogen metabolism in humans is discussed. NNAL and NNAL-Gluc are exceptionally useful biomarkers because they are derived from a carcinogen- 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)- that is specific to tobacco products. The NNAL assay has high sensitivity and specificity, which are particularly important for studies on ETS exposure. Other useful assays that have been widely applied involve quantitation of 1-HOP and tt-MA. Urinary carcinogen metabolite biomarkers will be critical components of future studies on tobacco and human cancer, particularly with respect to new tobacco products and strategies for harm reduction, the role of metabolic polymorphisms in cancer, and further evaluation of human carcinogen exposure from ETS.

Keywords: BaP, benzo[a]pyrene; ETS, environmental tobacco smoke; GC–TEA, gas chromatography with nitrosamine selective detection; 1-HOP, 1-hydroxypyrene; iso-NNAC, 4-(methylnitrosamino)-4-(3-pyridyl)butyric acid; NMTCA, N-nitroso-2-methylthiazolidine 4-carboxylic acid; NNAL, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol; NNAL-Gluc, a mixture of 4-(methylnitrosamino)-1-(3-pyridyl)-1-(O-β-d-glucopyranuronosyl)butane(NNAL-O-Gluc) and 4-(methylnitrosamino)-1-(3-pyridyl-N-β-d-glucopyranuronosyl)-1-butanolonium inner salt (NNAL-N-Gluc); NPRO, N-nitrosoproline; NSAR, N-nitrososarcosine; NTCA, N-nitrosothiazolidine 4-carboxylic acid; 8-oxo-dG, 8-oxodeoxyguanosine; PAH, polycyclic aromatic hydrocarbons; PhIP, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine; PREPS, potential reduced-exposure products; S-PMA, S-phenylmercapturic acid; trans-anti-BaP-tetraol, r-7,t-8,9,c-10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene; tt-MA, trans,trans-muconic acid.

Journal Article.  14006 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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