In vivo and in vitro metabolism of tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), by the freshwater planarian, Dugesia japonica

Wu, Jui-Pin; Li, Mei-Hui; Chen, Jhih-Sheng; Lee, Hui‐Ling

doi:10.1016/j.chemosphere.2012.02.024

Cited by 9 publications

(4 citation statements)

References 31 publications

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“…The concentrations of TSNAs, such as NNN and NNK, remained consistent pre- and post-consumption. The potential environmental risks caused by TSNAs in the aquatic environment are still limited [ 65 ] [ 66 ]. We observed limited HPHCs in the consumed WP tobacco from brand T9 ( i.e ., isoprene, phenol, FA).…”

Section: Discussionmentioning

confidence: 99%

Levels of Chemical Toxicants in Waterpipe Tobacco and Waterpipe Charcoal Solid Waste

Hsieh¹,

Mekoli²,

Edwards³

2021

JEP

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This work provides insights on waterpipe tobacco and waterpipe charcoal as potential sources of environmental toxicants. Selected harmful and potentially harmful constituents (HPHCs) from ten U.S. commercial waterpipe tobacco filler products (before and after electric heating) and five waterpipe charcoal products (before and after burning) were investigated. The differences in quantities of HPHCs between the evaluated products appear to be affected by raw material properties and/or the manufacturing processes involved in product production. Trace metal quantities in waterpipe tobacco and charcoal products were observed after heating or burning conditions compared to unheated or unburned conditions, which could impact the environment through the generation of toxic tobacco product waste. This study demonstrates that waterpipe tobacco and waterpipe charcoal contain substantial quantities of benzo[a]pyrene (B[a]P) and trace metals ( i.e ., selenium, arsenic, cadmium, chromium, cobalt, lead, nickel) before use and that extensive and varied changes in trace metal quantities take place as a result of heating, and more studies are needed to estimate the magnitude of the environmental impact of waterpipe tobacco use.

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Section: Discussionmentioning

confidence: 99%

Levels of Chemical Toxicants in Waterpipe Tobacco and Waterpipe Charcoal Solid Waste

Hsieh¹,

Mekoli²,

Edwards³

2021

JEP

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“…NNK is formed upon the oxidation of residual nicotine from tobacco smoke with nitrous acid, ozone, and other atmospheric oxidants (Sleiman et al, 2010). NNK has been ubiquitously detected in settled dust, even in some smoke-free homes (Ramírez et al, 2014), outdoor airborne particulate matter (Farren et al, 2015), waste waters (Lai et al, 2018) and river waters (Wu et al, 2012) expanding NNK exposure to non-smoking population such as children. Relevant NNK toxicity studies have traditionally focused on its associated carcinogenicity in adult animal models.…”

Section: Introductionmentioning

confidence: 99%

Toxicity of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NKK) in early development: a wide-scope metabolomics assay in zebrafish embryos

Merino

Casado

Piña

et al. 2021

Preprint

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The tobacco-specific nitrosamine 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a carcinogenic and ubiquitous environmental pollutant which carcinogenic and cytotoxic activity has been thoroughly investigated in murine models and human tissues. However, its potential deleterious effects on vertebrate early development are yet poorly understood. In this work, we characterized the impact of NNK exposure during early developmental stages of zebrafish embryos, a known alternative model for mammalian toxicity studies. Embryos exposed to different NNK concentrations were monitored for lethality and for the appearance of malformations during the first five days after fertilization. LC/MS-based untargeted metabolomics was subsequently performed for a wide-scope assay of NNK-related metabolic alterations. Our results revealed the presence of not only the parental compound, but also of two NKK known metabolites, 4-Hydroxy-4-(3-pyridyl)-butyric acid (HPBA) and 4-(Methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanol (NNAL-N-oxide) in exposed embryos likely resulting from active CYP450-mediated α-hydroxylation and NNK detoxification pathways, respectively. This was paralleled by a disruption in purine and pyrimidine metabolisms and the activation of the base excision repair pathway. Our results confirm NNK as a harmful embryonic agent and demonstrate zebrafish embryos to be a suitable early development model to monitor NNK toxicity.

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“…The effects of NNK and other tobacco constituents have typically been studied in mammalian systems [Wu et al, ]. However, these models are relatively expensive and slow to use, prompting the adoption of additional model organisms for such work.…”

Section: Introductionmentioning

confidence: 99%

The tobacco‐specific nitrosamine 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK) induces mitochondrial and nuclear DNA damage in Caenorhabditis elegans

Bodhicharla

Ryde

Prasad

et al. 2013

Environ and Mol Mutagen

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The metabolites of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) form DNA adducts in animal models. While there are many reports of formation of nuclear DNA adducts, one report also detected NNK-induced damage to the mitochondrial genome in rats. Using a different DNA damage detection technology, we tested whether this finding could be repeated in the nematode Caenorhabditis elegans. We treated N2 strain (wild-type) nematodes with NNK in liquid culture, and applied quantitative PCR to analyze NNK-induced nuclear and mitochondrial DNA (mtDNA) damage. Our results confirm that NNK causes both nuclear and mtDNA damage. However, we did not detect a difference in the level of nuclear versus mtDNA damage in C. elegans. To test whether the mtDNA damage was associated with mitochondrial dysfunction, we used a transgenic nematode strain that permits in vivo measurement of ATP levels and found lower levels of ATP in NNK-exposed animals when compared with the unexposed controls. To test whether the lower levels of ATP could be attributed to inhibition of respiratory chain components, we investigated oxygen consumption in whole C. elegans and found reduced oxygen consumption in exposed animals when compared with the unexposed controls. Our data suggest a model in which NNK exposure causes damage to both C. elegans nuclear and mitochondrial genomes, and support the hypothesis that the mitochondrial damage is functionally important in this model. These results also represent a first step in developing this genetically tractable organism as a model for assessing NNK toxicity.

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In vivo and in vitro metabolism of tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), by the freshwater planarian, Dugesia japonica

Cited by 9 publications

References 31 publications

Levels of Chemical Toxicants in Waterpipe Tobacco and Waterpipe Charcoal Solid Waste

Levels of Chemical Toxicants in Waterpipe Tobacco and Waterpipe Charcoal Solid Waste

Toxicity of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NKK) in early development: a wide-scope metabolomics assay in zebrafish embryos

The tobacco‐specific nitrosamine 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK) induces mitochondrial and nuclear DNA damage in Caenorhabditis elegans

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