Intraindividual and Interindividual Differences in Metabolites of the Tobacco-Specific Lung Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in Smokers' Urine

Steven G. Carmella, Shobha A. Akerkar, John Richie, Stephen S. Hecht

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

This study describes quantitation in smokers' urine of two metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-l-(3-pyridyl)-1 -butanone (NNK). The metabolites are 4-(methylnitrosamino)-l-(3-pyridyl)- 1-butanol (NNAL), which is also a lung carcinogen, and its O-glucuronide (NNAL-Gluc), a presumed detoxification product of NNK. Using updated methodology, levels of NNAL, NNAL-Gluc, and cotinine were determined in the urine of 61 smokers. The NNAL-Gluc:NNAL ratio, a potential marker for NNK detoxification potential, varied 16-fold in this group. Two phenotypes of this ratio were apparent; one ranging from 0 to 6 and found in 85% of the smokers and a second ranging from 6 to 11. The short-term and long-term consistency of the ratio was investigated. Studies carried out over a 4-5-day period indicated that the NNAL-Gluc: NNAL ratio was reasonably stable. Subjects who donated urine samples on two occasions separated by 4-16 months were classified in the same group (ratio range, 0-6 or 6-11) each time. Different urine collection protocols appeared to have little influence on the NNAL-Gluc:NNAL ratio. Thus, intraindividual differences in the NNAL-Gluc:NNAL ratio were generally small, whereas interindividual differences were large. Amounts of NNAL, NNAL-Gluc, and cotinine excreted by smokers were constant in 24-h samples obtained over a 3-day period of constant cigarette intake and controlled diet. Levels of NNAL, NNAL-Gluc, and NNAL plus NNAL-Gluc correlated with cotinine in a study of 61 smokers without controlled diet or smoking (r = 0.58; P < 0.0001). The results of this study indicate that urinary NNAL and NNAL-Gluc can be reliably quantified in smokers' urine, and that the NNAL-Gluc:NNAL ratio may be a useful biomarker for NNK detoxification in smokers.

Original languageEnglish (US)
Pages (from-to)635-642
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume4
Issue number6
StatePublished - Sep 1 1995

Fingerprint

Carcinogens
Tobacco
Urine
Lung
Cotinine
4-((methylnitrosoamino)-1-(3-pyridyl)but-1-yl)beta-omega-glucosiduronic acid
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
Butanones
Diet
Urine Specimen Collection
1-Butanol
Glucuronides
Tobacco Products
Biomarkers
Smoking
Phenotype

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Oncology

Cite this

@article{1ab1fd1e488b4f0d927bb570ab09ea2e,
title = "Intraindividual and Interindividual Differences in Metabolites of the Tobacco-Specific Lung Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in Smokers' Urine",
abstract = "This study describes quantitation in smokers' urine of two metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-l-(3-pyridyl)-1 -butanone (NNK). The metabolites are 4-(methylnitrosamino)-l-(3-pyridyl)- 1-butanol (NNAL), which is also a lung carcinogen, and its O-glucuronide (NNAL-Gluc), a presumed detoxification product of NNK. Using updated methodology, levels of NNAL, NNAL-Gluc, and cotinine were determined in the urine of 61 smokers. The NNAL-Gluc:NNAL ratio, a potential marker for NNK detoxification potential, varied 16-fold in this group. Two phenotypes of this ratio were apparent; one ranging from 0 to 6 and found in 85{\%} of the smokers and a second ranging from 6 to 11. The short-term and long-term consistency of the ratio was investigated. Studies carried out over a 4-5-day period indicated that the NNAL-Gluc: NNAL ratio was reasonably stable. Subjects who donated urine samples on two occasions separated by 4-16 months were classified in the same group (ratio range, 0-6 or 6-11) each time. Different urine collection protocols appeared to have little influence on the NNAL-Gluc:NNAL ratio. Thus, intraindividual differences in the NNAL-Gluc:NNAL ratio were generally small, whereas interindividual differences were large. Amounts of NNAL, NNAL-Gluc, and cotinine excreted by smokers were constant in 24-h samples obtained over a 3-day period of constant cigarette intake and controlled diet. Levels of NNAL, NNAL-Gluc, and NNAL plus NNAL-Gluc correlated with cotinine in a study of 61 smokers without controlled diet or smoking (r = 0.58; P < 0.0001). The results of this study indicate that urinary NNAL and NNAL-Gluc can be reliably quantified in smokers' urine, and that the NNAL-Gluc:NNAL ratio may be a useful biomarker for NNK detoxification in smokers.",
author = "Carmella, {Steven G.} and Akerkar, {Shobha A.} and John Richie and Hecht, {Stephen S.}",
year = "1995",
month = "9",
day = "1",
language = "English (US)",
volume = "4",
pages = "635--642",
journal = "Cancer Epidemiology Biomarkers and Prevention",
issn = "1055-9965",
publisher = "American Association for Cancer Research Inc.",
number = "6",

}

Intraindividual and Interindividual Differences in Metabolites of the Tobacco-Specific Lung Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in Smokers' Urine. / Carmella, Steven G.; Akerkar, Shobha A.; Richie, John; Hecht, Stephen S.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 4, No. 6, 01.09.1995, p. 635-642.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Intraindividual and Interindividual Differences in Metabolites of the Tobacco-Specific Lung Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in Smokers' Urine

AU - Carmella, Steven G.

AU - Akerkar, Shobha A.

AU - Richie, John

AU - Hecht, Stephen S.

PY - 1995/9/1

Y1 - 1995/9/1

N2 - This study describes quantitation in smokers' urine of two metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-l-(3-pyridyl)-1 -butanone (NNK). The metabolites are 4-(methylnitrosamino)-l-(3-pyridyl)- 1-butanol (NNAL), which is also a lung carcinogen, and its O-glucuronide (NNAL-Gluc), a presumed detoxification product of NNK. Using updated methodology, levels of NNAL, NNAL-Gluc, and cotinine were determined in the urine of 61 smokers. The NNAL-Gluc:NNAL ratio, a potential marker for NNK detoxification potential, varied 16-fold in this group. Two phenotypes of this ratio were apparent; one ranging from 0 to 6 and found in 85% of the smokers and a second ranging from 6 to 11. The short-term and long-term consistency of the ratio was investigated. Studies carried out over a 4-5-day period indicated that the NNAL-Gluc: NNAL ratio was reasonably stable. Subjects who donated urine samples on two occasions separated by 4-16 months were classified in the same group (ratio range, 0-6 or 6-11) each time. Different urine collection protocols appeared to have little influence on the NNAL-Gluc:NNAL ratio. Thus, intraindividual differences in the NNAL-Gluc:NNAL ratio were generally small, whereas interindividual differences were large. Amounts of NNAL, NNAL-Gluc, and cotinine excreted by smokers were constant in 24-h samples obtained over a 3-day period of constant cigarette intake and controlled diet. Levels of NNAL, NNAL-Gluc, and NNAL plus NNAL-Gluc correlated with cotinine in a study of 61 smokers without controlled diet or smoking (r = 0.58; P < 0.0001). The results of this study indicate that urinary NNAL and NNAL-Gluc can be reliably quantified in smokers' urine, and that the NNAL-Gluc:NNAL ratio may be a useful biomarker for NNK detoxification in smokers.

AB - This study describes quantitation in smokers' urine of two metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-l-(3-pyridyl)-1 -butanone (NNK). The metabolites are 4-(methylnitrosamino)-l-(3-pyridyl)- 1-butanol (NNAL), which is also a lung carcinogen, and its O-glucuronide (NNAL-Gluc), a presumed detoxification product of NNK. Using updated methodology, levels of NNAL, NNAL-Gluc, and cotinine were determined in the urine of 61 smokers. The NNAL-Gluc:NNAL ratio, a potential marker for NNK detoxification potential, varied 16-fold in this group. Two phenotypes of this ratio were apparent; one ranging from 0 to 6 and found in 85% of the smokers and a second ranging from 6 to 11. The short-term and long-term consistency of the ratio was investigated. Studies carried out over a 4-5-day period indicated that the NNAL-Gluc: NNAL ratio was reasonably stable. Subjects who donated urine samples on two occasions separated by 4-16 months were classified in the same group (ratio range, 0-6 or 6-11) each time. Different urine collection protocols appeared to have little influence on the NNAL-Gluc:NNAL ratio. Thus, intraindividual differences in the NNAL-Gluc:NNAL ratio were generally small, whereas interindividual differences were large. Amounts of NNAL, NNAL-Gluc, and cotinine excreted by smokers were constant in 24-h samples obtained over a 3-day period of constant cigarette intake and controlled diet. Levels of NNAL, NNAL-Gluc, and NNAL plus NNAL-Gluc correlated with cotinine in a study of 61 smokers without controlled diet or smoking (r = 0.58; P < 0.0001). The results of this study indicate that urinary NNAL and NNAL-Gluc can be reliably quantified in smokers' urine, and that the NNAL-Gluc:NNAL ratio may be a useful biomarker for NNK detoxification in smokers.

UR - http://www.scopus.com/inward/record.url?scp=0029089375&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029089375&partnerID=8YFLogxK

M3 - Article

VL - 4

SP - 635

EP - 642

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

SN - 1055-9965

IS - 6

ER -