title: Simultaneous determination of NNK and its metabolites in mouse tissue for evaluating the effects of chronic alcohol consumption on the metabolism of NNK in mouse liver and lung.
abstract: A hydrophilic-interaction liquid chromatography-tandem mass spectrometry (HILIC-MS-MS) method was developed for the determination of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its metabolites in mouse liver and lung. The limits of detection of all analytes were in the range 0.017-0.057 ng mL(-1), and recovery ranged from 88.4-119.8 % with intra and inter-day precision in the range 0.89-6.03 % and 1.01-6.97 %, respectively. This simple and accurate method was used to evaluate the effect of chronic alcohol consumption on NNK bioactivation in mouse tissue. Time-course curves for NNK and its metabolites were generated, and the areas under the curves (AUCs) were compared. It was found that target tissues of NNK carcinogenesis in C57BL/6 mice contained high levels of α-hydroxylation metabolites of NNK and its carbonyl reduction metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). The most pronounced effect of alcohol was to enhance α-hydroxylation of NNK in mouse lung and liver, which suggests that chronic alcohol consumption may increase the risk of carcinogenicity associated with NNK in mice.
authors.affiliation: Zhengzhou Tobacco Research Institute of CNTC, Zhengzhou, 450001, China.
authors.forename: Baojun
authors.initials: B
authors.lastname: Cao
authors.forename: Qidong
authors.initials: Q
authors.lastname: Zhang
authors.forename: Houwei
authors.initials: H
authors.lastname: Ji
authors.forename: Junhui
authors.initials: J
authors.lastname: Liu
authors.forename: Hailei
authors.initials: H
authors.lastname: Lang
authors.forename: Mingfei
authors.initials: M
authors.lastname: Feng
authors.forename: Jianxun
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000437:Alcoholism / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D019540:Area Under Curve; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D006900:Hydroxylation; D057230:Limit of Detection; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009602:Nitrosamines / Q000032:analysis* / Q000378:metabolism; D011725:Pyridines; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D009602:Nitrosamines; D011725:Pyridines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; C099565:4-(methylnitrosamino)-1-(3-pyridyl)-1-butan-1-ol