Metabolites of a Tobacco-specific Lung Carcinogen in the Urine of Elementary School-aged Children

Metabolites of a Tobacco-specific Lung Carcinogen in the Urine of Elementary School-aged Children1

University of Minnesota Cancer Center [S. S. H., M. Y., S. G. C.] and Division of Environmental and Occupational Health, School of Public Health [A. F., J. L. A., I. A. G., T. R. C., A. D. R., S. J. M., K. S.], University of Minnesota, Minneapolis, Minnesota 55455

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 ≥5 ng/ml. NNAL or NNAL-Gluc was detected in 52 of 54 samples with total cotinine ≥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.

Footnotes

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↵1 This study was supported by National Cancer Institute Grant CA-81301 and Science to Achieve Results Grants R825813 and R826789 from the United States Environmental Protection Agency. The Shared Resources are supported in part by National Cancer Institute Cancer Center Support Grant CA-77598.
↵2 To whom requests for reprints should addressed, at University of Minnesota Cancer Center, Mayo Mail Code 806, 420 Delaware Street S.E., Minneapolis, MN 55455. E-mail: hecht002{at}umn.edu
↵3 The abbreviations used are: ETS, environmental tobacco smoke; GC-MS/MS, gas chromatography-tandem mass spectrometry; GC-TEA, gas chromatography-nitrosamime selective detection; NNAL, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol; NNAL-Gluc, 4-(methylnitrosamino)-1-(3-pyridyl)-1-(O-β-d-glucopyranuronosyl)butane [some of the pyridine-N-glucuronide, 4-(methylnitrosamino)-1-(3-pyridyl-N-β-d-glucopyranuronosyl)-1-butanolonium inner salt, may also be present]; NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; SHIELD, School Health Initiative: Environment, Learning, Disease; HPLC, high-performance liquid chromatography; ID, inner diameter.
- Accepted September 11, 1901.
- Received April 20, 1901.
- Revision received July 27, 1901.