In vivo and in vitro metabolism of tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), by the freshwater planarian, Dugesia japonica |
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Authors: | Wu Jui-Pin Li Mei-Hui Chen Jhih-Sheng Lee Hui-Ling |
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Institution: | a Environmental Toxicology Laboratory, Department of Geography, National Taiwan University, 1, Section 4, Roosevelt Road, Taipei 106, Taiwan b Department of Chemistry, Fu Jen Catholic University, 510, Zhongzheng Road, Xinzhuang District, New Taipei City 24205, Taiwan |
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Abstract: | Cigarette smoke is a risk factor for human health, and many studies were conducted to investigate its adverse effects on humans and other mammals. However, since large amounts of cigarette products are produced and consumed, it is possible that tobacco chemicals can end up in aquatic environments through several routes, thus influencing aquatic organisms. In this study, the presence of tobacco-specific nitrosamine (TSNA), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), in aquatic environment was demonstrated. Since toxic effects on and distribution patterns of tobacco chemicals in aquatic organisms were rarely studied, after results of an acute toxicity pretest were obtained, experiment was conducted to investigate the bioaccumulation pattern of NNK and distribution patterns of its metabolites, mainly 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), in NNK-treated freshwater planarians, Dugesia japonica. Results from in vivo and in vitro studies showed that NNK was readily converted to NNAL through the carbonyl reduction in bodies of NNK-treated planarians. Tissue concentrations of both chemicals increased in time- and dose-dependent manners. Furthermore, we examined the end products of NNK/NNAL α-hydroxylation in NNK-treated planarians, but only 1-(3-pyridyl)-1,4-butanediol was detected, suggesting that NNK metabolism in planarians partially differs from that in mammalian systems. This is the first report on NNK metabolism in an aquatic organism and can be used as a foundation for developing freshwater planarians as a new in vivo model for the study of NNK toxicology in the future. |
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Keywords: | 11β-HSD 1 11β-hydroxysteroid dehydrogenase type 1 ANOVA analysis of variance CLi intrinsic clearance values CYP cytochrome P450 DEN N-nitrosodiethylamine DMN N-nitrosodimethylamine DMSO dimethyl sulfoxide G-6-P glucose-6-phosphate G-6-PD glucose-6-phosphate dehydrogenase HBA 4-hydroxy-4-(3-pyridyl)-butyric acid HPB 4-hydroxy-1-(3-pyridyl)-1-butanone HPLC-UV high-performance liquid chromatography coupled with UV detector LC-MS/MS liquid chromatography/tandem mass spectrometry LD50 medium lethal dose MFO mixed-function-oxidase NNAL 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol NNAL-Gluc NNAL-glucuronide NNK 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone NNN N&prime -nitrosonornicotine OBA 4-oxo-4-(3-pyridyl)-butyric acid PBD 1-(3-pyridyl)-1 4-butanediol SD standard deviation TSNAs tobacco-specific nitrosamines |
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