Metabolites of a tobacco-specific lung carcinogen in children exposed to secondhand or thirdhand tobacco smoke in their homes

Abstract

Background: People exposed to secondhand tobacco smoke (SHS) inhale the lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) which is metabolized to NNAL and its glucuroniders. These urinary metabolites, termed total NNAL, can be quantified. A related compound, iso-NNAL, has been proposed as a biomarker for exposure to smoke constituent residues on surfaces (thirdhand tobacco smoke). There is limited information in the literature on levels of total NNAL in children exposed to SHS.

Methods: We recruited 79 parent--child dyads from homes where the enrolled parent was a cigarette smoker and visited their homes. Parents were asked questions, home ambient air quality was evaluated, and children provided urine samples. Urine was analyzed for total NNAL, total cotinine, total nicotine, and iso-NNAL.

Results: Ninety percent of the children had detectable total NNAL in urine; total nicotine and total cotinine were also detected in most samples. There were significant positive relationships between biomarker levels and exposure of children in the home. Levels were highest in homes with no smoking restrictions. African American children had significantly higher levels than other children. iso-NNAL was not detected in any urine sample.

Conclusions: There was nearly universal exposure of children to the lung carcinogen NNK, due mainly to exposure to SHS from adult smokers in their homes.

Impact: Homes with adult smokers should adopt restrictions to protect their children from exposure to a potent lung carcinogen.

Figure 1

Summary of existing and proposed tobacco-specific carcinogen biomarkers for secondhand and thirdhand smoke exposure. Total NNAL (NNAL plus its glucuronides) is an established biomarker for uptake of the tobacco-specific lung carcinogen NNK in non-smokers exposed to secondhand smoke (SHS). The NNK comes from the sidestream smoke of a cigarette and the non-smoker is exposed to it by breathing air that contains sidestream smoke. iso-NNAL has been proposed as a biomarker of thirdhand smoke exposure because it is an expected metabolite of NNA, a compound formed on surfaces containing nicotine and exposed to nitrous acid (HONO). NNA is not known to be present in cigarette mainstream or sidestream smoke (11).

Figure 2

Frequency distributions of levels of urinary A) total NNAL, B) total cotinine, and C) total nicotine among the children in this study.

Figure 3

Chromatogram obtained upon analysis by gas chromatography-nitrosamine selective detection of the medium from human hepatocytes which had been incubated with NNA. The indicated peak is silylated iso-NNAL. The internal standard (I.S.) for the analysis was 5-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (C₅NNAL)

Figure 4

Typical chromatogram obtained upon analysis by gas chromatography-nitrosamine selective detection of urine from a child in this study. Arrow: retention time of silylated iso-NNAL. Peaks with arrows correspond to NNAL and two internal standards (I.S.) used in the analysis, C₅NNAL and N-nitrosopentyl-3-picolylamine (NPPA). Gas chromatography conditions are slightly different from those used for Figure 3.