國家衛生研究院 NHRI:Item 3990099045/3354
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/3354


    Title: Correlation between the urine profile of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone metabolites and N7-methylguanine in urothelial carcinoma patients
    Authors: Lee, HL;Hsueh, YM;Chung, CJ;Pu, YS;Chang, LW;Hsieh, DPH;Liou, SH;Lin, P
    Contributors: Division of Environmental Health and Occupational Medicine
    Abstract: A major carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is present in cigarette smoke and its metabolite, 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanol (NNAL), is used as an exposure biomarker for environmental tobacco smoke (ETS). This metabolite (NNAL) can be either detoxified into glucuronidated NNAL (NNAL-Gluc) or activated into an unstable reactive metabolite that methylates DNA along with formation of 4-hydroxy-4-(3-pyridyl)- butyric acid [hydroxy acid (HA)]. Therefore, the carcinogenic risk associated with ETS exposure is greatly modulated by individual variations in metabolic activation and detoxification capabilities. In this study, we defined the urinary HA/total NNAL [HA/total NNAL] ratio as the activation index and NNAL-Gluc/free NNAL [(total NNAL-free NNAL)/free NNAL] ratio as the detoxification index of NNK. The major methylated DNA adduct N 7-methylguanine (N7-MeG), considered as the carcinogenic biomarker for cigarette smoking, was excreted in urine. The objective of this study was to investigate the effects of these metabolic indexes of NNK on N 7-MeG urinary excretion in a population of urothelial carcinoma patients. Urinary levels of total NNAL (free NNAL plus NNAL-Gluc), free NNAL, HA, and N7-MeG were positively correlated with smoking. Furthermore, activation index and detoxification index correlated positively and negatively with N7-MeG levels, respectively. Our results suggest that these metabolic indices may represent the phenotype of individual metabolism capability and modulate the carcinogenic risk of ETS exposure.
    Date: 2008-12-01
    Relation: Cancer Epidemiology Biomarkers and Prevention. 2008 Dec 1;17(12):3390-3395.
    Link to: http://dx.doi.org/10.1158/1055-9965.epi-08-0761
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1055-9965&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000261724000016
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=57649137237
    Appears in Collections:[Pinpin Lin] Periodical Articles
    [Saou-Hsing Liou] Periodical Articles
    [Dennis P.H. Hsieh(2004-2007)] Periodical Articles
    [Louis W. Chang(1999-2009)] Periodical Articles

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