Selenomethionine inhibits ultraviolet radiation-induced p53 transactivation.
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 pRGCDeltafos-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 (approximately 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 microM 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.
Traynor
Nicola J
NJ
Photobiology Unit, Ninewells Hospital, University of Dundee, Dundee, UK.
McKenzie
Roddie C
RC
Beckett
Geoffrey J
GJ
Gibbs
Neil K
NK
D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D012645:Selenomethionine / Q000008:administration & dosage / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays
D011837:Radiation-Protective Agents; D016159:Tumor Suppressor Protein p53; D012645:Selenomethionine