https://scholars.lib.ntu.edu.tw/handle/123456789/544464
標題: | Correlation between the urine profile of 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanone metabolites and N7-methylguanine in urothelial carcinoma patients | 作者: | Lee H.-L. Hsueh Y.-M. Chung C.-J. YEONG-SHIAU PU Chang L.W. Hsieh D.P.H. Liou S.-H. Lin P. |
公開日期: | 2008 | 卷: | 17 | 期: | 12 | 起(迄)頁: | 3390-3395 | 來源出版物: | Cancer Epidemiology Biomarkers and Prevention | 摘要: | 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. Copyright ? 2008 American Association for Cancer Research. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-57649137237&doi=10.1158%2f1055-9965.EPI-08-0761&partnerID=40&md5=8191c68766f673866b5667080937950e https://scholars.lib.ntu.edu.tw/handle/123456789/544464 |
ISSN: | 1055-9965 | DOI: | 10.1158/1055-9965.EPI-08-0761 | SDG/關鍵字: | 4 (methylnitrosamino) 1 (3 pyridyl) 1 butanol; 4 (methylnitrosamino) 1 (3 pyridyl) 1 butanone; 7 methylguanine; glucuronide; adult; aged; article; cancer patient; cancer risk; carcinogenesis; cigarette smoking; controlled study; detoxification; DNA adduct; DNA methylation; female; human; major clinical study; male; metabolism; phenotype; priority journal; urinary excretion; urine level; urogenital tract cancer; Adult; Aged; Aged, 80 and over; Biological Markers; Carcinogens; Female; Guanine; Humans; Male; Middle Aged; Nitrosamines; Pyridines; Questionnaires; Smoking; Urinary Bladder Neoplasms |
顯示於: | 醫學系 |
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