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Selenomethionine inhibits ultraviolet radiation-induced p53 transactivation

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Abstract:

Background:

Ultraviolet (UV) radiation damages the cellular DNA of skin cells. In response, wild-type p53 protein accumulates in irradiated cells and the stabilized and transactivated protein can then induce genes involved in cell cycle arrest in G1, or in the initiation of apoptosis. Selenium protects cells from UVB-induced cell death and apoptosis by mechanisms which are unclear, although recent reports suggest that selenium protects against UV-induced cell damage by inducing DNA repair enzymes and transactivating p53. Methods:

We examined whether selenomethionine could protect human skin cells from UV radiation-induced p53 transactivation, using a pRGCΔfos-lacZ p53-dependent reporter construct stably transfected in an amelanotic melanoma cell line (Arn-8) which expresses wild-type p53. Cells were pretreated with or without selenomethionine and then irradiated with broadband UVB (∼270–350 nm); 0–30 mJ/cm2 from a Phillips TL100 W/12 lamp. Results:

The percentage of cells with transcriptionally active p53 increased dose dependently up to 20 mJ/cm2 UVB. Treatment with 50 M selenomethionine for 24 h both pre- and post-irradiation, significantly diminished p53 activation by 30–43% across the UV dose range (P=0.0085, n=5 independent experiments) and decreased UV-induced p53 protein accumulation as assessed by Western blotting. Conclusions:

We conclude that selenomethionine inhibits broad band UVB-induced p53 transactivation and protein accumulation and that this effect correlates with reported protective effects of selenium against UV-induced DNA damage.

Keywords: Arn-8 cells; p53; selenium; selenomethionine; ultraviolet radiation

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1600-0781.2006.00256.x

Affiliations: 1: Photobiology Unit, Ninewells Hospital, University of Dundee, Dundee, UK, Departments of 2: Veterinary Pathology, and 3: Clinical Biochemistry, University of Edinburgh, Edinburgh, UK and 4: Dermatological Sciences Research Group, University of Manchester Medical School, Manchester, UK

Publication date: December 1, 2006

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