Protection against ultraviolet radiation involves MC1R-mediated non-pigmentary and pigmentary mechanisms in vivo
Robinson, Samantha, Dixon, Sandra, August, Suzannah, Diffey, Brian, Wakamatsu, Kazumasa, Ito, Shosuke, Friedmann, Peter S. and Healy, Eugene (2010) Protection against ultraviolet radiation involves MC1R-mediated non-pigmentary and pigmentary mechanisms in vivo. Journal of Investigative Dermatology, 130, (7), 1904-1913. (doi:10.1038/jid.2010.48). (PMID:20237490).
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Individuals with red hair and fair skin due to MC1R gene variants are at higher risk of cutaneous neoplasia, consistent with MC1R having a role in photoprotection. The exact reasons for greater UVR susceptibility as a result of compromised MC1R function are unclear, but hypotheses include reduced photoprotection due to less eumelanin, pheomelanin-induced phototoxicity, and lower protection by “non-pigmentary” MC1R effects. To determine how MC1R photoprotects, an in vivo hairless MC1R model containing Mc1r?/? albino, MC1R+Mc1r?/? albino, Mc1r?/? pigmented, and MC1R+Mc1r?/? pigmented mice was generated. After single doses of UVR, no significant differences in epidermal cyclobutane pyrimidine dimers or sunburn cell (SBC) formation were observed between pigmented and albino groups. However, after repeated UVR exposure, the number of p53 clones in albino skin was significantly elevated when this was null for MC1R. Furthermore, in the absence of functional MC1R, fewer p53 clones were observed in pigmented than in albino skin. The results indicate that MC1R protects by a combination of pigmentary and non-pigmentary effects in vivo and that when MC1R function is compromised the melanin type in skin is still protective against UVR.
|Digital Object Identifier (DOI):||doi:10.1038/jid.2010.48|
|Subjects:||R Medicine > RL Dermatology
Q Science > QH Natural history > QH426 Genetics
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
|Divisions:||University Structure - Pre August 2011 > School of Medicine > Infection, Inflammation and Repair
|Date Deposited:||02 Mar 2010|
|Last Modified:||31 Mar 2016 13:05|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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