Protection against UVR 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.
Dermatopharmacology, University of Southampton, Southampton, Hampshire, UK.
Samantha
S
Robinson
Sandra
S
Dixon
Suzannah
S
August
Brian
B
Diffey
Kazumasa
K
Wakamatsu
Shosuke
S
Ito
Peter S
PS
Friedmann
Eugene
E
Healy
D000818:Animals; D016923:Cell Death / Q000528:radiation effects; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D004487:Edema / Q000473:pathology / Q000517:prevention & control; D004817:Epidermis / Q000502:physiology / Q000528:radiation effects*; D006801:Humans; D008543:Melanins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D008822:Mice, Transgenic; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics* / Q000378:metabolism*; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D012880:Skin Pigmentation / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
D008543:Melanins; D044102:Receptor, Melanocortin, Type 1; D016159:Tumor Suppressor Protein p53; C018362:pheomelanin; C041877:eumelanin