| Correlation between the urine profile of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone metabolites and N7-methylguanine in urothelial carcinoma patients. | |
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MedLine Citation:
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PMID: 19064555 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 (N(7)-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 N(7)-MeG were positively correlated with smoking. Furthermore, activation index and detoxification index correlated positively and negatively with N(7)-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. |
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Authors:
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Hui-Ling Lee; Yu-Mei Hsueh; Chi-Jung Chung; Yeong-Shiau Pu; Louis W Chang; Dennis Paul Hsientang Hsieh; Saou-Hsing Liou; Pinpin Lin |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Volume: 17 ISSN: 1055-9965 ISO Abbreviation: Cancer Epidemiol. Biomarkers Prev. Publication Date: 2008 Dec |
Date Detail:
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Created Date: 2008-12-09 Completed Date: 2009-01-27 Revised Date: 2009-01-31 |
Medline Journal Info:
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Nlm Unique ID: 9200608 Medline TA: Cancer Epidemiol Biomarkers Prev Country: United States |
Other Details:
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Languages: eng Pagination: 3390-5 Citation Subset: IM |
Affiliation:
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Division of Environmental Health and Occupational Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan Town, Miaoli County, Taiwan 350. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Aged, 80 and over Biological Markers / urine Carcinogens / metabolism* Female Guanine / analogs & derivatives*, urine Humans Male Middle Aged Nitrosamines / urine* Pyridines / urine* Questionnaires Smoking / adverse effects* Urinary Bladder Neoplasms / urine* |
| Chemical | |
Reg. No./Substance:
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0/4-(methylnitrosamino)-1-(3-pyridyl)-1-butan-1-ol; 0/Biological Markers; 0/Carcinogens; 0/Nitrosamines; 0/Pyridines; 578-76-7/7-methylguanine; 64091-91-4/4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; 73-40-5/Guanine |
| Comments/Corrections | |
Erratum In:
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Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):361 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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