This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Van Schooten, F. J. Articles by Van Zandwijk, N. Search for Related Content PubMed PubMed Citation Articles by Van Schooten, F. J. Articles by Van Zandwijk, N.

Effects of Oral Administration of N-Acetyl-L-cysteine

A Multi-Biomarker Study in Smokers

Departments of Health Risk Analysis and Toxicology [F. J. V. S., A. B. N., J. W. D.] and Pharmacology and Toxicology [A. B., G. R. M. M. H.], Maastricht University, 6200 MD, Maastricht, the Netherlands; Department of Health Sciences, University of Genoa, I-16132 Genoa, Italy [S. D. F., F. D., A. I., A. C.]; Departments of Otolaryngology [A. J. M. B.], Molecular Pathology [L. V. V.], and Thoracic Oncology [P. B., N. V. Z.], The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands; and Department of Thoracic Surgery, Tokyo Medical University College, Tokyo, Japan [H. S.]

N-Acetyl-L-cysteine (NAC) has been shown to exert cancer-protective mechanisms and effects in experimental models. We report here the results of a randomized, double-blind, placebo-controlled, Phase II chemoprevention trial with NAC in healthy smoking volunteers. The subjects were supplemented daily with 2 x 600 mg of oral tablets of NAC (n = 20) or placebo (n = 21) for a period of 6 months, and internal dose markers [plasma and bronchoalveolar lavage (BAL) fluid cotinine, urine mutagenicity], biologically effective dose markers [smoking-related DNA adducts and hemoglobin (Hb) adducts], and biological response markers (micronuclei frequency and antioxidants scavenging capacity) were assessed at both pre- and postsupplementation times (T₀ and T₁, respectively). Overall, the internal dose markers remained unchanged at T₁ as compared with T₀ in both NAC and placebo groups. When quantifying the biologically effective dose markers, we observed an inhibitory effect of NAC toward the formation of lipophilic-DNA adducts (5.18 ± 0.73 versus 4.08 ± 1.03/10⁸ nucleotides; mean ± SE; P = 0.05) as well as of 7,8-dihydro-8-oxo-2'-deoxyguanosine adducts in BAL cells (3.9 ± 0.6 versus 2.3 ± 0.2/10⁵ nucleotides; P = 0.003). There was no effect of NAC on the formation of lipophilic-DNA adducts in peripheral blood lymphocytes or polycyclic aromatic hydrocarbon-DNA adducts in mouth floor/buccal mucosa cells or 4-aminobiphenyl-Hb adducts. Likewise, quantification of the biological response markers showed an inhibitory effect of NAC on the frequency of micronuclei in mouth floor and in soft palate cells (1.3 ± 0.2 versus 0.9 ± 0.2; P = 0.001) and a stimulating effect of NAC on plasma antioxidant scavenging capacity (393 ± 14 versus 473 ± 19 µM Trolox; P = 0.1) but not on BAL fluid antioxidant scavenging capacity. We conclude that NAC has the potential to impact upon tobacco smoke carcinogenicity in humans because it can modulate certain cancer-associated biomarkers in specific organs.

This article has been cited by other articles:

				S. Bonassi, B. Biasotti, M. Kirsch-Volders, S. Knasmueller, E. Zeiger, S. Burgaz, C. Bolognesi, N. Holland, P. Thomas, M. Fenech, et al. State of the art survey of the buccal micronucleus assay--a first stage in the HUMNXL project initiative Mutagenesis, July 1, 2009; 24(4): 295 - 302. [Abstract] [Full Text] [PDF]

				I. Rahman Review: Antioxidant therapeutic advances in COPD Therapeutic Advances in Respiratory Disease, December 1, 2008; 2(6): 351 - 374. [Abstract] [PDF]

				J.-P. Coppe, M. Boysen, C. H. Sun, B. J.F. Wong, M. K. Kang, N.-H. Park, P.-Y. Desprez, J. Campisi, and A. Krtolica A Role for Fibroblasts in Mediating the Effects of Tobacco-Induced Epithelial Cell Growth and Invasion Mol. Cancer Res., July 1, 2008; 6(7): 1085 - 1098. [Abstract] [Full Text] [PDF]

				S. Bonassi, A. Znaor, M. Ceppi, C. Lando, W. P. Chang, N. Holland, M. Kirsch-Volders, E. Zeiger, S. Ban, R. Barale, et al. An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans Carcinogenesis, March 1, 2007; 28(3): 625 - 631. [Abstract] [Full Text] [PDF]

				R. Reliene and R. H. Schiestl Antioxidants Suppress Lymphoma and Increase Longevity in Atm-Deficient Mice J. Nutr., January 1, 2007; 137(1): 229S - 232S. [Abstract] [Full Text] [PDF]

				I. Rahman and I. M. Adcock Oxidative stress and redox regulation of lung inflammation in COPD. Eur. Respir. J., July 1, 2006; 28(1): 219 - 242. [Abstract] [Full Text] [PDF]

				M. J. Kelley, E. M. Glaser, J. E. Herndon II, F. Becker, R. Bhagat, Y.-J. Zhang, R. M. Santella, S. G. Carmella, S. S. Hecht, L. Gallot, et al. Safety and Efficacy of Weekly Oral Oltipraz in Chronic Smokers Cancer Epidemiol. Biomarkers Prev., April 1, 2005; 14(4): 892 - 899. [Abstract] [Full Text] [PDF]

				K. R. Sekhar, P. A. Crooks, V. N. Sonar, D. B. Friedman, J. Y. Chan, M. J. Meredith, J. H. Starnes, K. R. Kelton, S. R. Summar, S. Sasi, et al. NADPH Oxidase Activity Is Essential for Keap1/Nrf2-mediated Induction of GCLC in Response to 2-Indol-3-yl-methylenequinuclidin-3-ols Cancer Res., September 1, 2003; 63(17): 5636 - 5645. [Abstract] [Full Text] [PDF]