ReviewChemical research in toxicology2017
Context Matters: Contribution of Specific DNA Adducts to the Genotoxic Properties of the Tobacco-Specific Nitrosamine NNK.
Review in Chemical research in toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
28 citing papers in PubMed, 52 citations in OpenAlex.
- The complexity of tobacco smoke-induced mutagenesis in head and neck cancer.Nature genetics · 2025Article
- 5-(Pyridin-3-yl)-3,4-dihydro-2Royal Society open science · 2024Article
- The repertoire of mutational signatures in tobacco- and non-tobacco-induced oral cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- Dissection of Cancer Mutational Signatures with Individual Components of Cigarette Smoking.Chemical research in toxicology · 2023Article
- Risk assessment ofEFSA journal. European Food Safety Authority · 2023Article
- Identification of Formaldehyde-Induced DNA-RNA Cross-Links in the A/J Mouse Lung Tumorigenesis Model.Chemical research in toxicology · 2022Article
- Nicotine Inhibits the Cytotoxicity and Genotoxicity of NNK Mediated by CYP2A13 in BEAS-2B Cells.Molecules (Basel, Switzerland) · 2022Article
- Metabolism and DNA Adduct Formation of Tobacco-SpecificInternational journal of molecular sciences · 2022Review
- Smokeless tobacco and cigarette smoking: chemical mechanisms and cancer prevention.Nature reviews. Cancer · 2022Review
- 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone provokes progression from chronic pancreatitis to pancreatic intraepithelial neoplasia.iScience · 2022Article
- Physico-chemical properties of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) diazonium ion: a theoretical investigation.RSC advances · 2021Article
- Urinary biomarkers for secondhand smoke and heated tobacco products exposure.Journal of clinical biochemistry and nutrition · 2021Article
- Regulatory function of peroxiredoxin I on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung cancer development.Oncology letters · 2021Review
- Alkylating and oxidative stresses in smoking and non-smoking patients with COPD: Implications for lung carcinogenesis.Free radical biology & medicine · 2021Article
- Prenatal stress enhances NNK-induced lung tumors in A/J mice.Carcinogenesis · 2020Article
- Effects of smoking cessation on biological monitoring markers in urine.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2020Article
- Methyl DNA phosphate adduct formation in lung tumor tissue and adjacent normal tissue of lung cancer patients.Carcinogenesis · 2019Article
- Physical binding of the tobacco smoke carcinogen NNK diazonium ion to the human tumor suppressor gene TP53 Exon 5.Toxicology research · 2019Article
- Quantification of DNA Lesions Induced by 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol in Mammalian Cells.Chemical research in toxicology · 2019Article
- Review
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Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent pulmonary carcinogen in laboratory animals. It is classified as a Group 1 human carcinogen by the International Agency for Cancer Research. NNK is bioactivated upon cytochrome P450 catalyzed hydroxylation of the carbon atoms adjacent to the nitrosamino group to both methylating and pyridyloxobutylating agents. Both pathways generate a spectrum of DNA damage that contributes to the overall mutagenic and toxic properties of this compound. NNK is also reduced to form 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), which is also carcinogenic. Like NNK, NNAL requires metabolic activation to DNA alkylating agents. Methyl hydroxylation of NNAL generates pyridylhydroxybutyl DNA adducts, and methylene hydroxylation leads to DNA methyl adducts. The consequence of this complex metabolism is that NNK generates a vast spectrum of DNA damage, any form of which can contribute to the overall carcinogenic properties of this potent pulmonary carcinogen. This Perspective reviews the chemistry and genotoxic properties of the collection of DNA adducts formed from NNK. In addition, it provides evidence that multiple adducts contribute to the overall carcinogenic properties of this chemical. The adduct that contributes to the genotoxic effects of NNK depends on the context, such as the relative amounts of each DNA alkylating pathway occurring in the model system, the levels and genetic variants of key repair enzymes, and the gene targeted for mutation.
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