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| Content Provider | PubMed Central |
|---|---|
| Author | Cotter, Murray A. Thomas, Joshua Cassidy, Pamela Robinette, Kyle Jenkins, Noah Scott, R. Florell Leachman, Sancy Samlowski, Wolfram E. Grossman, Douglas |
| Abstract | UV radiation is the major environmental risk factor for melanoma and a potent inducer of oxidative stress, which is implicated in the pathogenesis of several malignancies. We evaluated whether the thiol antioxidant N-acetylcysteine (NAC) could protect melanocytes from UV-induced oxidative stress/damage in vitro and from UV-induced melanoma in vivo. In melan-a cells, a mouse melanocyte line, NAC (1–10 mM) conferred protection from several UV-induced oxidative sequelae including production of intracellular peroxide, formation of the signature oxidative DNA lesion 8-oxoguanine (8-OG), and depletion of free reduced thiols (primarily glutathione). Mice transgenic for hepatocyte growth factor and Survivin, previously shown to develop melanoma following a single neonatal dose of UV irradiation, were administered NAC (7 mg/ml, mother’s drinking water) transplacentally and through nursing until two weeks after birth. Delivery of NAC in this manner reduced thiol depletion and blocked formation of 8-OG in skin following neonatal UV treatment. Mean onset of UV-induced melanocytic tumors was significantly delayed in NAC-treated compared to control mice (21 vs. 14 weeks, p=0.0003). Our data highlight the potential importance of oxidative stress in the pathogenesis of melanoma, and suggest that NAC may be useful as a chemopreventive agent. |
| Related Links | http://dx.doi.org/10.1158/1078-0432.CCR-07-1187 |
| Starting Page | 5952 |
| File Format | |
| ISSN | 10780432 |
| Journal | Clinical cancer research : an official journal of the American Association for Cancer Research |
| Issue Number | 19 |
| Volume Number | 13 |
| Language | English |
| Publisher Date | 2007-10-01 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Oncology |
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