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详细内容
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4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a tobacco-specific nitrosamine carcinogen.1 Reactive metabolites of NNK alkylate DNA, forming pyridyloxobutyl (POB) and pyridylhydroxybutyl (PHB) adducts, and induce DNA methylation. NNK (100 mg/kg, single dose) increases the protein levels of DNA methyltransferase 1 (DNMT1) in mouse bronchial epithelial cells within one day and increases hypermethylation of the tumor suppressor genes Chd13, Prdm2, and Runx3 in lung tissue within three days.2 It induces tumor formation preferentially in the lung via various routes of administration in animal models.3 NNK induces adenomas and adenocarcinomas, which are present after 16 and 50 weeks, respectively, in mouse lung when administered at a single dose of 10 μmol/animal. Lifetime administration of NNK (63.5 mg/animal) to rats results in a 90% incidence of lung tumors.4
1.Carlson, E.S., Upadhyaya, P., Villalta, P.W., et al.Analysis and identification of 2’-deoxyadenosine-derived adducts in lung and lover DNA of F-344 rats treated with the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and enantiomers of its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanolChem. Res. Toxicol.31(5)358-370(2018) 2.Jin, H., Chen, J.X., Wang, H., et al.NNK-induced DNA methyltransferase 1 in lung tumorigenesis in A/J mice and inhibitory effects of (-)-epigallocatechin-3-gallateNutr. Cancer67(1)167-176(2016) 3.Hecht, S.S.Biochemistry, biology, and carcinogenicity of tobacco-specific N-nitrosaminesChem. Res. Toxicol.11(6)559-603(1998) 4.Rivenson, A., Hoffmann, D., Prokopczyk, B., et al.Induction of lung and exocrine pancreas tumors in F344 rats by tobacco-specific and Areca-derived N-nitrosaminesCancer Res.48(23)6912-6917(1988)
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