In vivo and in vitro metabolism of tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), by the freshwater planarian, Dugesia japonica
Journal
Chemosphere
Journal Volume
87
Journal Issue
11
Pages
1341-1347
Date Issued
2012
Author(s)
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. © 2012.
Subjects
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL); 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK); Aquatic organism; Carbonyl reduction; Planarian; Tobacco-specific nitrosamine (TSNA)
Other Subjects
Biochemistry; Chemicals; Health risks; Ketones; Mammals; Metabolism; Metabolites; Smoke; Tobacco; Water; 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL); 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK); Carbonyl reduction; Planarian; Tobacco specific nitrosamines; Aquatic organisms; 1 (3 pyridyl) 1,4 butanediol; 4 (methylnitrosamino) 1 (3 pyridyl) 1 butanol; 4 (methylnitrosamino) 1 (3 pyridyl) 1 butanone; carbonyl reductase; nitrosamine; unclassified drug; aquatic organism; bioaccumulation; carbonyl compound; chemical pollutant; dose-response relationship; flatworm; freshwater ecosystem; metabolism; public health; risk factor; smoking; tobacco; toxicity test; toxicology; acute toxicity; animal experiment; aquatic environment; article; bioaccumulation; carbonylation; concentration response; controlled study; Dugesia japonica; hydroxylation; metabolism; nonhuman; tissue level; tobacco; Turbellaria; Dugesia japonica; Mammalia; Nicotiana tabacum; Planaria; Turbellaria
Type
journal article