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Protection against ultraviolet radiation involves MC1R-mediated non-pigmentary and pigmentary mechanisms in vivo

Protection against ultraviolet radiation involves MC1R-mediated non-pigmentary and pigmentary mechanisms in vivo
Protection against ultraviolet radiation involves MC1R-mediated non-pigmentary and pigmentary mechanisms in vivo
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.
0022-202X
1904-1913
Robinson, Samantha
4ef22161-0375-4d64-a699-6c9e33cd174a
Dixon, Sandra
8ae67493-b245-4abd-aff1-a3852a8ec5b2
August, Suzannah
1fc940e8-45d7-46b0-8da7-efdfcfcbebbb
Diffey, Brian
b70ab8ae-4f4d-477a-9284-4b7dfcb059af
Wakamatsu, Kazumasa
07556397-5692-416f-a156-f1059ec5f8d3
Ito, Shosuke
9b4ffa79-82f4-4f04-ab64-359663fdc1a7
Friedmann, Peter S.
d50bac23-f3ec-4493-8fa0-fa126cbeba88
Healy, Eugene
400fc04d-f81a-474a-ae25-7ff894be0ebd
Robinson, Samantha
4ef22161-0375-4d64-a699-6c9e33cd174a
Dixon, Sandra
8ae67493-b245-4abd-aff1-a3852a8ec5b2
August, Suzannah
1fc940e8-45d7-46b0-8da7-efdfcfcbebbb
Diffey, Brian
b70ab8ae-4f4d-477a-9284-4b7dfcb059af
Wakamatsu, Kazumasa
07556397-5692-416f-a156-f1059ec5f8d3
Ito, Shosuke
9b4ffa79-82f4-4f04-ab64-359663fdc1a7
Friedmann, Peter S.
d50bac23-f3ec-4493-8fa0-fa126cbeba88
Healy, Eugene
400fc04d-f81a-474a-ae25-7ff894be0ebd

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)

Record type: Article

Abstract

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.

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Published date: July 2010
Organisations: Infection Inflammation & Immunity

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Local EPrints ID: 73139
URI: http://eprints.soton.ac.uk/id/eprint/73139
ISSN: 0022-202X
PURE UUID: f3710bb6-34ae-4168-b404-754f24b33419

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Date deposited: 02 Mar 2010
Last modified: 13 Mar 2024 21:55

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Contributors

Author: Samantha Robinson
Author: Sandra Dixon
Author: Suzannah August
Author: Brian Diffey
Author: Kazumasa Wakamatsu
Author: Shosuke Ito
Author: Peter S. Friedmann
Author: Eugene Healy

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