4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a tobacco-specific nitrosamine carcinogen.{45973} 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.{45974} It induces tumor formation preferentially in the lung via various routes of administration in animal models.{45975} 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.{45976}