Document Detail

Correlation between the urine profile of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone metabolites and N7-methylguanine in urothelial carcinoma patients.
MedLine Citation:
PMID:  19064555     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
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:
Created Date:  2008-12-09     Completed Date:  2009-01-27     Revised Date:  2009-01-31    
Medline Journal Info:
Nlm Unique ID:  9200608     Medline TA:  Cancer Epidemiol Biomarkers Prev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3390-5     Citation Subset:  IM    
Division of Environmental Health and Occupational Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan Town, Miaoli County, Taiwan 350.
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MeSH Terms
Aged, 80 and over
Biological Markers / urine
Carcinogens / metabolism*
Guanine / analogs & derivatives*,  urine
Middle Aged
Nitrosamines / urine*
Pyridines / urine*
Smoking / adverse effects*
Urinary Bladder Neoplasms / urine*
Reg. No./Substance:
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
Erratum In:
Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):361

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