The nitrosation of nicotine: a kinetic study

Ws, Caldwell; Jm, Greene; Dr, Plowchalk; Jd, deBethizy

doi:10.1021/tx00023a003

Cited by 25 publications

(12 citation statements)

References 10 publications

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“…One potential pathway to 1 is the oxidation and nitrosation of nicotine by nitrite. 9,10 Another possible alkaloid precursor of 1 is pseudooxynicotine (2), an intermediate formed by microbial degradation of nicotine 11,12 and also as an autoxidation product of nicotine, 13 which is efficiently nitrosated to 1 in the presence of nitrous acid. 14 While the TSNAs in mainstream cigarette smoke derive at least in part from the distillation of these preformed nitrosamines in tobacco, another fraction of mainstream cigarette smoke TSNAs is formed during combustion of the tobacco by nitrosation of the respective alkaloid precursors, possibly with nitrogen oxides originating from nitrate, which is present in high concentrations in some tobacco types.…”

mentioning

confidence: 99%

Matrix-Bound 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone in Tobacco: Quantification and Evidence for an Origin from Lignin-Incorporated Alkaloids

Lang

Vuarnoz

2014

J. Nat. Prod.

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Substantial quantities of the carcinogenic tobacco-specific N-nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (1; NNK) are still found in the mainstream smoke of tobacco exhaustively extracted with water, indicating the presence of an insoluble, matrix-bound form. Soluble and matrix-bound concentrations of 1 in tobacco were determined by applying a new method using sequential aqueous extraction at room temperature and at 130 °C. On average, 77% and 53% of the total content of 1 were matrix-bound in air-cured (Burley type) and flue-cured tobaccos, respectively. Thermal release of 1 from its matrix-bound form above ca. 200 °C can account for a large fraction of its concentration in cigarette mainstream smoke. An already matrix-bound alkaloid precursor of matrix-bound 1 was identified in vascular tissue of green leaf midribs. The incubation of vascular cell-wall preparations with the lignin precursor coniferyl alcohol and isotopically labeled nicotine or pseudooxynicotine (2) led to the formation of labeled matrix-bound 1 after nitrosation, suggesting that incorporation of nicotine or its oxidized product 2 during lignin polymerization is the origin of the formation of matrix-bound 1.

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mentioning

confidence: 99%

Matrix-Bound 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone in Tobacco: Quantification and Evidence for an Origin from Lignin-Incorporated Alkaloids

Lang

Vuarnoz

2014

J. Nat. Prod.

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“…After reducing the nicotine content of tobacco leaves by grafting technology, the aroma quality and quantity, undesirable taste, impact, irritancy, satisfaction, pleasure, and acceptance decreased. Nicotine and alkaloids are the precursors of TSNAs, and there is a direct correlation between tobacco alkaloids and TSNAs [19,20]. There was a significant positive correlation between the content of TSNAs and alkaloids in tobacco leaves under the same conditions of nitrate nitrogen content and a modulating environment [21].…”

Section: Discussionmentioning

confidence: 99%

Reducing the nicotine content of tobacco by grafting with eggplant

et al. 2020

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Background: Nicotine is a stimulant and potent parasympathomimetic alkaloid that accounts for 96-98% of alkaloid content. A reduction in the amount of nicotine in cigarettes to achieve a non-addictive level is necessary. We investigated whether replacing tobacco root with eggplant by grafting can restrict nicotine biosynthesis and produce tobacco leaves with ultra-low nicotine content, and analyzed the gene expression differences induced by eggplant grafting. Results: The nicotine levels of grafted tobacco leaves decreased dramatically. The contents of nornicotine, anabasine, NNN, NNK, NAT, total TSNAs and the nicotine of mainstream cigarette smoke decreased, and the contents of amino acids and the precursors of alkaloids increased in grafted tobacco. Eggplant grafting resulted in the differential expression of 440 genes. LOC107774053 had higher degrees in two PPI networks, which were regulated by LOC107802531 and LOC107828746 in the TF-target network. Conclusions: Replacing tobacco root with eggplant by grafting can restrict nicotine biosynthesis and produce tobacco leaves with ultra-low or zero nicotine content. The differential expression of LOC107774053 may be associated with eggplant grafting.

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“…Some scientists have hypothesized that ingested tobacco alkaloids, such as nicotine, might contribute to TSNA formation within the human body (Hoffmann et al 1994; Hecht and Hoffmann 1989). Others have published data that support the conclusion that endogenous TSNA formation does not occur (Fischer et al 1990; Caldwell et al 1991; Meger et al 1995; Adlkofer 1995; Spiegelhalder and Fischer 1990; Hecht et al 1999; Tricker et al 1993). The hypothesis of endogenous TSNA formation conflicts with recent evidence that smoking cessation therapies that involve the administration of nicotine in the form of gum, patch, and/or inhalers do not lead to endogenous TSNA formation (Hecht et al 1999).…”

Section: Nnk and Other Tsna In Tobacco And Tobacco Smokementioning

confidence: 92%

An Analysis of the Role of Tobacco-Specific Nitrosamines in the Carcinogenicity of Tobacco Smoke

Brown

Borschke

Doolittle

2003

Nonlinearity in Biology, Toxicology, Medicine

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Cigarette smoke is a complex mixture consisting of more than 4500 chemicals, including several tobacco-specific nitrosamines (TSNA). TSNA typically form in tobacco during the post-harvest period, with some fraction being transferred into mainstream smoke when a cigarette is burned during use. The most studied of the TSNA is 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). NNK has been shown to be carcinogenic in laboratory animals. Studies examining the carcinogenicity of NNK frequently are conducted by injecting rodents with a single dose of 2.5 to 10 mumol of pure NNK; the amount of NNK contained in all of the mainstream smoke from about 3700 to 14,800 typical U.S. cigarettes. Extrapolated to a 70-kg smoker, the carcinogenic dose of pure NNK administered to rodents would be equivalent to the amount of NNK in all of the mainstream smoke of 22 to 87 million typical U.S. cigarettes. Furthermore, extrapolating results from rodent studies based on a single injection of pure NNK to establish a causative role for NNK in the carcinogenicity of chronic tobacco smoke exposure in humans is not consistent with basic pharmacological and toxicological principles. For example, such an approach fails to consider the effect of other smoke constituents upon the toxicity of NNK. In vitro studies demonstrate that nicotine, cotinine, and aqueous cigarette "tar" extract (ACTE) all inhibit the mutagenic activity of NNK. In vivo studies reveal that the formation of pulmonary DNA adducts in mice injected with NNK is inhibited by the administration of cotinine and mainstream cigarette smoke. Cigarette smoke has been shown to modulate the metabolism of NNK, providing a mechanism for the inhibitory effects of cigarette smoke and cigarette smoke constituents on NNK-induced tumorigenesis. NNK-related pulmonary DNA adducts have not been detected in rodents exposed to cigarette smoke, nor has the toxicity of tobacco smoke or tobacco smoke condensate containing marked reductions in TSNA concentrations been shown to be reduced in any biological assay. In summary, there is no experimental evidence to suggest that reduction of TSNA will reduce the mutagenic, cytotoxic, or carcinogenic potential of tobacco smoke.

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The nitrosation of nicotine: a kinetic study

Cited by 25 publications

References 10 publications

Matrix-Bound 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone in Tobacco: Quantification and Evidence for an Origin from Lignin-Incorporated Alkaloids

Matrix-Bound 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone in Tobacco: Quantification and Evidence for an Origin from Lignin-Incorporated Alkaloids

Reducing the nicotine content of tobacco by grafting with eggplant

An Analysis of the Role of Tobacco-Specific Nitrosamines in the Carcinogenicity of Tobacco Smoke

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