Involvement of Nicotine and Its Metabolites in the Pathology of Smoking-Related Diseases: Facts and Hypotheses

Adlkofer, F.

doi:10.1007/978-3-0348-7445-8_3

Cited by 2 publications

(3 citation statements)

References 22 publications

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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%

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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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Section: Nnk and Other Tsna In Tobacco And Tobacco Smokementioning

confidence: 92%

“…1991;Meger ei at. 1995;Adlkofer 1995;Spiegelhalder and Fischer 1990;Hecht ei at. 1999;Tricker et at.…”

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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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“…All these effects are presumably evoked by the release of a variety of neurotransmitters after activation of nicotinic cholinergic receptors by nicotine ( Benowitz, 2008 ). On the other hand, there is no scientific evidence that, for healthy adults, nicotine is involved in the major smoking and tobacco use-related diseases such as cancer, CVD and COPD ( Adlkofer, 1995 , Benowitz, 1997 ).…”

Section: Introductionmentioning

confidence: 99%

Assessment of nicotine delivery and uptake in users of various tobacco/nicotine products

Scherer

Mütze

Pluym

et al. 2022

Current Research in Toxicology

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Involvement of Nicotine and Its Metabolites in the Pathology of Smoking-Related Diseases: Facts and Hypotheses

Cited by 2 publications

References 22 publications

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

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

Assessment of nicotine delivery and uptake in users of various tobacco/nicotine products

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