title: A Phase II Randomized Placebo-Controlled Trial of Oral N-acetylcysteine for Protection of Melanocytic Nevi against UV-Induced Oxidative Stress In Vivo.
abstract: Oxidative stress plays a role in UV-induced melanoma, which may arise from melanocytic nevi. We investigated whether oral administration of the antioxidant N-acetylcysteine (NAC) could protect nevi from oxidative stress in vivo in the setting of acute UV exposure. The minimal erythemal dose (MED) was determined for 100 patients at increased risk for melanoma. Patients were randomized to receive a single dose (1,200 mg) of NAC or placebo, in double-blind fashion, and then one nevus was irradiated (1-2 MED) using a solar simulator. One day later, the MED was redetermined and the irradiated nevus and a control unirradiated nevus were removed for histologic analysis and examination of biomarkers of NAC metabolism and UV-induced oxidative stress. Increased expression of 8-oxoguanine, thioredoxin reductase-1, and γ-glutamylcysteine synthase modifier subunit were consistently seen in UV-treated compared with unirradiated nevi. However, no significant differences were observed in these UV-induced changes or in the pre- and postintervention MED between those patients receiving NAC versus placebo. Similarly, no significant differences were observed in UV-induced changes between subjects with germline wild-type versus loss-of-function mutations in the melanocortin-1 receptor. Nevi showed similar changes of UV-induced oxidative stress in an open-label post-trial study in 10 patients who received NAC 3 hours before nevus irradiation. Thus, a single oral dose of NAC did not effectively protect nevi from UV-induced oxidative stress under the conditions examined. Cancer Prev Res; 10(1); 36-44. ©2016 AACR.
authors.affiliation: Department of Dermatology, Oregon Health & Science University, Portland, Oregon. doug.grossman@hci.utah.edu cassidyp@ohsu.edu.|Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
authors.forename: Pamela B
authors.initials: PB
authors.lastname: Cassidy
authors.affiliation: Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, Utah.
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Dermatology, University of Utah Health Sciences Center, Salt Lake City, Utah.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Florell
authors.affiliation: Department of Dermatology, Oregon Health & Science University, Portland, Oregon.
authors.forename: Matthew
authors.initials: M
authors.lastname: Honeggar
authors.affiliation: Department of Dermatology, Oregon Health & Science University, Portland, Oregon.|Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
authors.forename: Sancy A
authors.initials: SA
authors.lastname: Leachman
authors.affiliation: Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, Utah.|Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Boucher
authors.affiliation: Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, Utah. doug.grossman@hci.utah.edu cassidyp@ohsu.edu.|Department of Dermatology, University of Utah Health Sciences Center, Salt Lake City, Utah.|Department of Oncological Sciences, University of Utah Health Sciences Center, Salt Lake City, Utah.
authors.forename: Douglas
authors.initials: D
authors.lastname: Grossman
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D000284:Administration, Oral; D000975:Antioxidants / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D004311:Double-Blind Method; D005721:Glutamate-Cysteine Ligase / Q000032:analysis; D006147:Guanine / Q000031:analogs & derivatives / Q000032:analysis; D006801:Humans; D008545:Melanoma / Q000209:etiology / Q000517:prevention & control*; D009154:Mutation; D009508:Nevus, Pigmented / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D010865:Pilot Projects; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics; D012878:Skin Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D013472:Sunlight / Q000009:adverse effects; D054481:Thioredoxin Reductase 1 / Q000032:analysis; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D044102:Receptor, Melanocortin, Type 1; C024829:8-hydroxyguanine; D006147:Guanine; C516124:TXNRD1 protein, human; D054481:Thioredoxin Reductase 1; C546365:GCLM protein, human; D005721:Glutamate-Cysteine Ligase; D000111:Acetylcysteine