Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Clin Cancer Res. 2007 Oct 1;13(19):5952-8.

N-acetylcysteine protects melanocytes against oxidative stress/damage and delays onset of ultraviolet-induced melanoma in mice.

Author information

  • 1Department of Dermatology, Huntsman Cancer Institute, Salt Lake City, Utah 84112, USA.

Abstract

PURPOSE:

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.

EXPERIMENTAL DESIGN:

In vitro experiments used the mouse melanocyte line melan-a. For in vivo experiments, mice transgenic for hepatocyte growth factor and survivin, shown previously to develop melanoma following a single neonatal dose of UV irradiation, were given NAC (7 mg/mL; mother's drinking water) transplacentally and through nursing until 2 weeks after birth.

RESULTS:

NAC (1-10 mmol/L) protected melan-a cells from several UV-induced oxidative sequelae, including production of intracellular peroxide, formation of the signature oxidative DNA lesion 8-oxoguanine, and depletion of free reduced thiols (primarily glutathione). Delivery of NAC reduced thiol depletion and blocked formation of 8-oxoguanine in mouse skin following neonatal UV treatment. Mean onset of UV-induced melanocytic tumors was significantly delayed in NAC-treated compared with control mice (21 versus 14 weeks; P = 0.0003).

CONCLUSIONS:

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.

PMID:
17908992
[PubMed - indexed for MEDLINE]
PMCID:
PMC2409148
Free PMC Article

Images from this publication.See all images (4)Free text

Figure 1
Figure 2
Figure 3
Figure 4
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk