Cancer Epidemiology Biomarkers & Prevention, Vol 5, Issue 7 521-525, Copyright © 1996 by American Association for Cancer Research

ARTICLES

Metabolites of a tobacco-specific nitrosamine, 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanone (NNK), in the urine of smokeless tobacco users: relationship between urinary biomarkers and oral leukoplakia

LA Kresty, SG Carmella, A Borukhova, SA Akerkar, R Gopalakrishnan, RE Harris, GD Stoner and SS Hecht
Department of Preventive Medicine, Ohio State University, Columbus, USA.

Two metabolites of the carcinogenic tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone were quantified in the urine of smokeless tobacco users. The metabolites are 4-(methylnitrosamino) -1-(3-pyridyl)-1-butanol (NNAL) and [4-(methylnitrosamino)-1-(3-pyridyl) but-1-yl]-beta-O-D-glucosiduronic acid (NNAL-Gluc). The study population consisted of 47 male nonsmokers, of whom 23 were snuff dippers, 13 were tobacco chewers, 3 were users of both products, and 8 were nonusers. The levels of NNAL-Gluc in urine ranged from 0.14-30.3 pmol/mg creatinine with a mean +/- SD of 3.47 +/- 5.86, whereas the levels of NNAL ranged from 0.02-8.73 pmol/mg creatinine with a mean +/- SD of 0.92 +/- 1.59. The mean levels of NNAL-Gluc and NNAL were not significantly different from those measured in a previous study of smokers. The levels of NNAL-Gluc were significantly higher in snuff dippers than in tobacco chewers. The ratio of NNAL-Gluc:NNAL was higher in snuff dippers than in tobacco chewers or smokers. There was no indication of two phenotypes of the NNAL-Gluc:NNAL ratio in smokeless tobacco users, in contrast to previous observations in smokers. Of the 39 smokeless tobacco users in this study, 16 presented with oral leukoplakia. When the total levels of NNAL-Gluc, NNAL, or NNAL-Gluc + NNAL were divided into tertiles, there was a significant association between the presence of leukoplakia and increasing levels of these metabolites; a similar relationship was found between urinary cotinine and leukoplakia. The results of this study demonstrate that there is significant uptake of carcinogenic nitrosamines in smokeless tobacco users, and that such products are not harmless alternatives to cigarettes. Moreover, the urinary biomarkers NNAL-Gluc, NNAL, and cotinine were associated with the presence of leukoplakia, which provides biochemical support for the role of smokeless tobacco products as a cause of oral leukoplakia.

This article has been cited by other articles:

				S. S. Hecht, S. G. Carmella, S. E. Murphy, W. T. Riley, C. Le, X. Luo, M. Mooney, and D. K. Hatsukami Similar Exposure to a Tobacco-Specific Carcinogen in Smokeless Tobacco Users and Cigarette Smokers Cancer Epidemiol. Biomarkers Prev., August 1, 2007; 16(8): 1567 - 1572. [Abstract] [Full Text] [PDF]

				S. S. Hecht Tobacco Carcinogen Biomarkers: Old and New Am. Assoc. Cancer Res. Educ. Book, April 1, 2005; 2005(1): 85 - 88. [Full Text] [PDF]

				S. S. Hecht Human urinary carcinogen metabolites: biomarkers for investigating tobacco and cancer Carcinogenesis, June 1, 2002; 23(6): 907 - 922. [Abstract] [Full Text] [PDF]

				S. S. Hecht, S. G. Carmella, M. Ye, K.-a. Le, J. A. Jensen, C. L. Zimmerman, and D. K. Hatsukami Quantitation of Metabolites of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone after Cessation of Smokeless Tobacco Use Cancer Res., January 1, 2002; 62(1): 129 - 134. [Abstract] [Full Text] [PDF]

				P. Upadhyaya, P. M.J. Kenney, J. B. Hochalter, M. Wang, and S. S. Hecht Tumorigenicity and metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol enantiomers and metabolites in the A/J mouse Carcinogenesis, August 1, 1999; 20(8): 1577 - 1582. [Abstract] [Full Text] [PDF]