Effects of oral administration of N-acetyl-L-cysteine: A multi-biomarker study in smokers

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...

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Published in:Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2002-02, Vol.11 (2), p.167-175
Main Authors: VAN SCHOOTEN, Frederik Jan, AHMAD BESARATI NIA, VAN'T VEER, Laura, BAAS, Paul, SAKAI, Harumasa, VAN ZANDWIJK, Nico, DE FLORA, Silvio, D'AGOSTINI, Francesco, IZZOTTI, Alberto, CAMOIRANO, Anna, BALM, Alfons J. M, DALLINGA, Jan Willem, BAST, Aalt, HAENEN, Guido R. M. M
Format: Article
Language:English
Subjects:
Acetylcysteine - administration & dosage
Acetylcysteine - therapeutic use
Administration, Oral
Adult
Anticarcinogenic Agents - administration & dosage
Anticarcinogenic Agents - therapeutic use
Antineoplastic agents
Antioxidants - administration & dosage
Antioxidants - therapeutic use
Biological and medical sciences
Biomarkers - analysis
Carcinogenesis, carcinogens and anticarcinogens
Chemical agents
Chemotherapy
Cotinine - metabolism
DNA Adducts
DNA Damage
Double-Blind Method
Female
Free Radical Scavengers - administration & dosage
Free Radical Scavengers - therapeutic use
Humans
Male
Medical sciences
Mutagenicity Tests
Neoplasms - etiology
Neoplasms - prevention & control
Pharmacology. Drug treatments
Smoking - adverse effects
Smoking - metabolism
Tumors
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Summary: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 (T(0) and T(1), respectively). Overall, the internal dose markers remained unchanged at T(1) as compared with T(0) 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 +/- 1.03/10(8) 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 +/- 0.2/10(5) 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 microM 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.
ISSN:1055-9965
1538-7755