Effect of differing levels of tobacco-specific nitrosamines in cigarette smoke on the levels of biomarkers in smokers.
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.
Ashley
David L
DL
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia 30341, USA. dla1@cdc.gov
O'Connor
Richard J
RJ
Bernert
John T
JT
Watson
Clifford H
CH
Polzin
Gregory M
GM
Jain
Ram B
RB
Hammond
David
D
Hatsukami
Dorothy K
DK
Giovino
Gary A
GA
Cummings
K Michael
KM
McNeill
Ann
A
Shahab
Lion
L
King
Bill
B
Fong
Geoffrey T
GT
Zhang
Liqin
L
Xia
Yang
Y
Yan
Xizheng
X
McCraw
Joan M
JM
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
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