Cancer Epidemiology Biomarkers & Prevention, Vol 6, Issue 7 517-522, Copyright © 1997 by American Association for Cancer Research

ARTICLES

Effects of indole-3-carbinol on the metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in smokers

E Taioli, S Garbers, HL Bradlow, SG Carmella, S Akerkar and SS Hecht
New York University Medical Center, New York 10012, USA.

Indole-3-carbinol (I3C) is a component of the human diet, occurring as a conjugate in certain cruciferous vegetables. I3C protects against carcinogenesis in a variety of animal models by modifying carcinogen metabolism. In mice, I3C decreases lung tumor formation by the tobacco-specific nitrosamine 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by enhancing its hepatic clearance (M. A. Morse et al., Cancer Res., 50: 2613-2617, 1990). In this study, our goal was to determine whether I3C would have similar effects on NNK metabolism in smokers as it did in mice. Thirteen women took 400 mg of I3C on 5 consecutive days and maintained constant smoking habits during this period. Their urine was analyzed before and after the I3C treatment period for two metabolites of NNK: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide (NNAL-Gluc). I3C treatment resulted in decreased levels of urinary NNAL, NNAL-Gluc, and NNAL plus NNAL-Gluc, and increased NNAL-Gluc:NNAL ratio in 10 of the 13 women. The mean decreases in NNAL (-0.27 +/- 0.09 pmol/mg creatinine, -23.4%) and NNAL plus NNAL-Gluc (-0.43 +/- 0.16 pmol/mg creatinine, -10.9%) were statistically significant as was the increase in NNAL-Gluc:NNAL ratio (1.1 +/- 0.5, 39.9%). These changes in urinary metabolites of NNK were consistent with those seen in mice treated with I3C and NNK; they suggest that I3C increased hepatic metabolism of NNK in our smokers. This is the first study to examine the effects of I3C on metabolism of an exogenous carcinogen in humans.

This article has been cited by other articles:

				J. H. Lubin, N. Caporaso, D. K. Hatsukami, A. M. Joseph, and S. S. Hecht The Association of a Tobacco-Specific Biomarker and Cigarette Consumption and Its Dependence on Host Characteristics Cancer Epidemiol. Biomarkers Prev., September 1, 2007; 16(9): 1852 - 1857. [Abstract] [Full Text] [PDF]

				Y. Weng, C. Fang, R. J. Turesky, M. Behr, L. S. Kaminsky, and X. Ding Determination of the Role of Target Tissue Metabolism in Lung Carcinogenesis Using Conditional Cytochrome P450 Reductase-Null Mice Cancer Res., August 15, 2007; 67(16): 7825 - 7832. [Abstract] [Full Text] [PDF]

				F. Kassie, L. B. Anderson, R. Scherber, N. Yu, D. Lahti, P. Upadhyaya, and S. S. Hecht Indole-3-carbinol Inhibits 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone Plus Benzo(a)pyrene-Induced Lung Tumorigenesis in A/J Mice and Modulates Carcinogen-Induced Alterations in Protein Levels Cancer Res., July 1, 2007; 67(13): 6502 - 6511. [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, S. G. Carmella, P. M.J. Kenney, S.-H. Low, K. Arakawa, and M. C. Yu Effects of Cruciferous Vegetable Consumption on Urinary Metabolites of the Tobacco-Specific Lung Carcinogen 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone in Singapore Chinese Cancer Epidemiol. Biomarkers Prev., June 1, 2004; 13(6): 997 - 1004. [Abstract] [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]

				J. W Lampe Health effects of vegetables and fruit: assessing mechanisms of action in human experimental studies Am. J. Clinical Nutrition, September 1, 1999; 70(3): 475S - 490. [Abstract] [Full Text] [PDF]