Hecht Stephen S
University of Minnesota Cancer Center, Minneapolis, MN 55455, USA.
Carcinogenesis. 2002 Jun;23(6):907-22. doi: 10.1093/carcin/23.6.907.
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.
测量人体尿液中的致癌物代谢物是获取有关烟草与癌症重要信息的一种实用方法。本综述介绍了目前可用的方法并评估了它们的实用性。已在吸烟者或接触环境烟草烟雾（ETS）的非吸烟者尿液中定量的致癌物及其代谢物和相关化合物包括反式、反式粘康酸（tt-MA）和S-苯基巯基尿酸（苯的代谢物）、1-萘酚和2-萘酚、羟基菲和菲二氢二醇、1-羟基芘（1-HOP）、苯并[a]芘的代谢物、芳香胺和杂环芳香胺、N-亚硝基脯氨酸、4-（甲基亚硝基氨基）-1-（3-吡啶基）-1-丁醇及其葡萄糖醛酸苷（NNAL和NNAL-葡萄糖醛酸苷）、8-氧代脱氧鸟苷、硫醚、巯基尿酸和烷基腺嘌呤。亚硝胺及其代谢物也已在无烟烟草使用者的尿液中定量。讨论了这些检测方法在提供致癌物剂量信息、区分暴露与未暴露个体以及人类致癌物代谢方面的实用性。NNAL和NNAL-葡萄糖醛酸苷是特别有用的生物标志物，因为它们源自一种特定于烟草制品的致癌物——4-（甲基亚硝基氨基）-1-（3-吡啶基）-1-丁酮（NNK）。NNAL检测具有高灵敏度和特异性，这对于ETS暴露研究尤为重要。其他已广泛应用的有用检测方法包括1-HOP和tt-MA的定量。尿液致癌物代谢物生物标志物将是未来烟草与人类癌症研究的关键组成部分，特别是在新型烟草制品和减少危害策略、代谢多态性在癌症中的作用以及进一步评估ETS导致的人类致癌物暴露方面。
