title: Effect of differing levels of tobacco-specific nitrosamines in cigarette smoke on the levels of biomarkers in smokers.
abstract: BACKGROUND
  Smokers are exposed to significant doses of carcinogens, including tobacco-specific nitrosamines (TSNA). Previous studies have shown significant global differences in the levels of TSNAs in cigarette smoke because of the variation in tobacco blending and curing practices around the world.
  
  
  METHODS
  Mouth-level exposure to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) measured in cigarette butts and urinary concentrations of its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) were examined among 126 daily smokers in four countries over a 24-hour study period.
  
  
  RESULTS
  As mouth-level exposure of NNK increased, the urinary NNAL increased even after adjustment for other covariates (beta = 0.46, P = 0.004). The relationship between mouth-level exposure to nicotine and its salivary metabolite, cotinine, was not statistically significant (beta = 0.29, P = 0.057), likely because of the very limited range of differences in mouth-level nicotine exposure in this population.
  
  
  CONCLUSIONS
  We have shown a direct association between the 24-hour mouth-level exposure of NNK resulting from cigarette smoking and the concentration of its primary metabolite, NNAL, in the urine of smokers. Internal dose concentrations of urinary NNAL are significantly lower in smokers in countries that have lower TSNA levels in cigarettes such as Canada and Australia in contrast to countries that have high levels of these carcinogens in cigarettes, such as the United States.
  
  
  CONCLUSIONS
  Lowering the levels of NNK in the mainstream smoke of cigarettes through the use of specific tobacco types and known curing practices can significantly affect the exposure of smokers to this known carcinogen.
authors.affiliation: Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia 30341, USA. dla1@cdc.gov
authors.forename: David L
authors.initials: DL
authors.lastname: Ashley
authors.forename: Richard J
authors.initials: RJ
authors.lastname: O'Connor
authors.forename: John T
authors.initials: JT
authors.lastname: Bernert
authors.forename: Clifford H
authors.initials: CH
authors.lastname: Watson
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Polzin
authors.forename: Ram B
authors.initials: RB
authors.lastname: Jain
authors.forename: David
authors.initials: D
authors.lastname: Hammond
authors.forename: Dorothy K
authors.initials: DK
authors.lastname: Hatsukami
authors.forename: Gary A
authors.initials: GA
authors.lastname: Giovino
authors.forename: K Michael
authors.initials: KM
authors.lastname: Cummings
authors.forename: Ann
authors.initials: A
authors.lastname: McNeill
authors.forename: Lion
authors.initials: L
authors.lastname: Shahab
authors.forename: Bill
authors.initials: B
authors.lastname: King
authors.forename: Geoffrey T
authors.initials: GT
authors.lastname: Fong
authors.forename: Liqin
authors.initials: L
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Xia
authors.forename: Xizheng
authors.initials: X
authors.lastname: Yan
authors.forename: Joan M
authors.initials: JM
authors.lastname: McCraw
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism / Q000652:urine; D003367:Cotinine / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000378:metabolism; D009602:Nitrosamines / Q000032:analysis / Q000378:metabolism* / Q000652:urine; D011725:Pyridines / Q000032:analysis / Q000378:metabolism; D012463:Saliva / Q000378:metabolism; D012907:Smoking / Q000378:metabolism* / Q000652:urine; D055815:Young Adult; D014026:Nicotiana
chemical_list: D015415:Biomarkers; D009602:Nitrosamines; D011725:Pyridines; D009538:Nicotine; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; C099565:4-(methylnitrosamino)-1-(3-pyridyl)-1-butan-1-ol; D003367:Cotinine