Data from Use of Oral <i>N</i>-Acetylcysteine for Protection of Melanocytic Nevi against UV-Induced Oxidative Stress: Towards a Novel Paradigm for Melanoma Chemoprevention

Abstract

<div>Abstract<p><b>Purpose:</b> Induction of oxidative stress has been implicated in UV-induced melanoma. We sought to determine whether the antioxidant <i>N</i>-acetylcysteine (NAC) could be safely administered to protect melanocytic nevi from the oxidative stress resulting from acute UV exposure.</p><p><b>Experimental Design:</b> Patients at increased risk for melanoma were recruited from a screening clinic. Induction and detection of oxidative stress (reactive oxygen species and glutathione depletion) was optimized in nevi following <i>ex vivo</i> UV irradiation. Nevi were removed from patients before, and following, oral ingestion of a single (1,200 mg) dose of NAC, and then these nevi were UV irradiated (4,000 J/m<sup>2</sup>).</p><p><b>Results:</b> Oxidative stress was induced in nevi 24 to 48 hours following <i>ex vivo</i> UV irradiation. A single oral dose of NAC was well tolerated in all patients (<i>n</i> = 72). Basal levels of reduced glutathione and the NAC metabolite cysteine were well correlated between similar-appearing nevi from the same patient and were significantly increased in nevi removed 3 hours after NAC ingestion compared with nevi removed before drug ingestion. In approximately half (9 of 19) of patients tested, UV-induced glutathione depletion was attenuated in the postdrug (compared with predrug) nevus.</p><p><b>Conclusions:</b> NAC can be safely administered to patients for the purpose of modulating UV-induced oxidative stress in nevi. This study suggests the feasibility of patients taking NAC prophylactically before acute UV exposure, to prevent pro-oncogenic oxidative stress in nevi and ultimately reduce long-term melanoma risk. (Clin Cancer Res 2009;15(23):7434–40)</p></div>