title: 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone is correlated with 8-hydroxy-2'-deoxyguanosine in humans after exposure to environmental tobacco smoke.
abstract: Cigarette smoking and exposure to environmental tobacco smoke (ETS) are important risk factors for many cancers. However, exposure doses have usually not been quantitatively assessed in human studies. In humans 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronate conjugate (defined as total NNAL) are the major metabolites of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, a cigarette-specific carcinogen. Although animal studies have shown that exposure to cigarette smoke increases tissue oxidative DNA damage, the relationship between cigarette smoke and 8-hydroxydeoxyguanosine (8-OHdG) is not consistent in human studies. In the present study, we have developed a simple, sensitive, and robust LC-MS/MS method for quantifying total NNAL and 8-OHdG concentrations in human plasma. We quantified total NNAL and 8-OHdG in plasma as well as 8-OHdG in urine of 121 healthy male subjects. Total NNAL levels were significantly higher in ever-smokers than in never-smokers. Furthermore, total NNAL levels in plasma were increased with numbers of cigarettes smoked per day in ever-smokers. It suggests that total NNAL in plasma is a good biomarker for cigarette smoke exposure. After stratifying by smoking status and adjusting for age, ETS exposure and occupation category, total NNAL was associated with plasma and urinary 8-OHdG in never-smokers, but not in ever-smokers. Since total NNAL levels in nonsmokers represented the ETS exposure, it appears that 8-OHdG levels are dose-dependently correlated with their ETS exposure dose. Furthermore, this correlation supports the hypothesis that oxidative DNA damage is one of major adverse effects induced by ETS exposure in humans.
authors.affiliation: Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli County, Taiwan, ROC.
authors.forename: Hung-Che
authors.initials: HC
authors.lastname: Chiang
authors.forename: Yung-Kai
authors.initials: YK
authors.lastname: Huang
authors.forename: Pei-Fen
authors.initials: PF
authors.lastname: Chen
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Chang
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Wang
authors.forename: Pinpin
authors.initials: P
authors.lastname: Lin
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Lee
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000367:Age Factors; D015415:Biomarkers / Q000097:blood*; D002853:Chromatography, Liquid / Q000379:methods; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000097:blood / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure; D006801:Humans; D008297:Male; D009602:Nitrosamines / Q000097:blood*; D012907:Smoking / Q000009:adverse effects*; D018709:Statistics, Nonparametric; D053719:Tandem Mass Spectrometry / Q000379:methods; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D015415:Biomarkers; D009602:Nitrosamines; D014028:Tobacco Smoke Pollution; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine