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

Abstract

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 × 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.