Use of oral N-acetylcysteine for protection of melanocytic nevi against UV-induced oxidative stress: towards a novel paradigm for melanoma chemoprevention.
OBJECTIVE
Induction of oxidative stress has been implicated in UV-induced melanoma. We sought to determine whether the antioxidant N-acetylcysteine (NAC) could be safely administered to protect melanocytic nevi from the oxidative stress resulting from acute UV exposure.


METHODS
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 ex vivo 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(2)).


RESULTS
Oxidative stress was induced in nevi 24 to 48 hours following ex vivo UV irradiation. A single oral dose of NAC was well tolerated in all patients (n = 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.


CONCLUSIONS
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.
Goodson
Agnessa Gadeliya
AG
Department of Dermatology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA.
Cotter
Murray A
MA
Cassidy
Pamela
P
Wade
Mark
M
Florell
Scott R
SR
Liu
Tong
T
Boucher
Kenneth M
KM
Grossman
Douglas
D
D000111:Acetylcysteine / Q000008:administration & dosage*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D000975:Antioxidants / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008297:Male; D008545:Melanoma / Q000517:prevention & control*; D008875:Middle Aged; D009508:Nevus, Pigmented / Q000188:drug therapy*; D018384:Oxidative Stress; D012306:Risk; D012878:Skin Neoplasms / Q000517:prevention & control*; D013997:Time Factors; D014466:Ultraviolet Rays
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D005978:Glutathione; D003545:Cysteine; D000111:Acetylcysteine