title: Metabolites of a tobacco-specific lung carcinogen in the urine of elementary school-aged children.
abstract: Limited data are available in the literature on carcinogen uptake by children exposed to environmental tobacco smoke (ETS). In this study, we quantified metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in the urine of elementary school-aged children participating in the School Health Initiative: Environment, Learning, Disease study, a school-based investigation of the environmental health of children. The metabolites of NNK are 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide (NNAL-Gluc). We also measured cotinine and its glucuronide (total cotinine). Urine samples were collected from 204 children. Seventy (34.3%) of these had total cotinine > or =5 ng/ml. NNAL or NNAL-Gluc was detected in 52 of 54 samples with total cotinine > or =5 ng/ml and in 10 of 20 samples with total cotinine < 5 ng/ml. Levels of NNAL plus NNAL-Gluc and total cotinine were significantly higher when exposure to ETS was reported than when no exposure was reported. However, even when no exposure to ETS was reported, levels of NNAL, NNAL-Gluc, and NNAL plus NNAL-Gluc were higher than in children with documented low exposure to ETS, as determined by cotinine levels < 5 ng/ml. Levels of NNAL, NNAL-Gluc, and cotinine were not significantly different in samples collected twice from the same children at 3-month intervals. Levels of NNAL plus NNAL-Gluc in this study were comparable with those observed in our previous field studies of adults exposed to ETS. There was a 93-fold range of NNAL plus NNAL-Gluc values in the exposed children. The results of this study demonstrate widespread and considerable uptake of the tobacco-specific lung carcinogen NNK in this group of elementary school-aged children, raising important questions about potential health risks. Our data indicate that objective biomarkers of carcinogen uptake are important in studies of childhood exposure to ETS and cancer later in life.
authors.affiliation: University of Minnesota Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA. hecht002@umn.edu
authors.forename: S S
authors.initials: SS
authors.lastname: Hecht
authors.forename: M
authors.initials: M
authors.lastname: Ye
authors.forename: S G
authors.initials: SG
authors.lastname: Carmella
authors.forename: A
authors.initials: A
authors.lastname: Fredrickson
authors.forename: J L
authors.initials: JL
authors.lastname: Adgate
authors.forename: I A
authors.initials: IA
authors.lastname: Greaves
authors.forename: T R
authors.initials: TR
authors.lastname: Church
authors.forename: A D
authors.initials: AD
authors.lastname: Ryan
authors.forename: S J
authors.initials: SJ
authors.lastname: Mongin
authors.forename: K
authors.initials: K
authors.lastname: Sexton
mesh_terms: D015415:Biomarkers / Q000652:urine*; D002273:Carcinogens / Q000378:metabolism*; D002648:Child; D003367:Cotinine / Q000031:analogs & derivatives* / Q000652:urine; D004784:Environmental Monitoring; D005260:Female; D005965:Glucuronates / Q000652:urine*; D006801:Humans; D008297:Male; D009602:Nitrosamines / Q000378:metabolism* / Q000652:urine*; D014028:Tobacco Smoke Pollution
chemical_list: C099564:4-((methylnitrosoamino)-1-(3-pyridyl)but-1-yl)beta-omega-glucosiduronic acid; D015415:Biomarkers; D002273:Carcinogens; D005965:Glucuronates; D009602:Nitrosamines; D014028:Tobacco Smoke Pollution; C075991:cotinine N-glucuronide; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D003367:Cotinine