Dermatopharmacology, University of Southampton, Southampton, Hampshire, UK.
J Invest Dermatol. 2010 Jul;130(7):1904-13. doi: 10.1038/jid.2010.48. Epub 2010 Mar 18.
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.
由于 MC1R 基因突变，红发和白皙皮肤的个体患有皮肤肿瘤的风险更高，这与 MC1R 在光保护中发挥作用一致。由于 MC1R 功能受损导致 UVR 敏感性增加的确切原因尚不清楚，但假设包括由于黑色素较少导致光保护减少、褐黑素诱导的光毒性以及“非色素”MC1R 效应的保护作用降低。为了确定 MC1R 如何进行光保护，生成了一种含有 Mc1r(-/-)白化、MC1R(+)Mc1r(-/-)白化、Mc1r(-/-)色素沉着和 MC1R(+)Mc1r(-/-)色素沉着的无毛 MC1R 模型。在单次 UVR 剂量后，色素沉着和白化组之间的表皮环丁烷嘧啶二聚体或晒伤细胞 (SBC) 形成没有明显差异。然而，在重复 UVR 暴露后，当 MC1R 缺失时，白化皮肤中的 p53 克隆数量显着增加。此外，在缺乏功能性 MC1R 的情况下，色素沉着皮肤中的 p53 克隆比白化皮肤中少。结果表明，MC1R 通过体内色素和非色素效应的组合进行保护，并且当 MC1R 功能受损时，皮肤中的黑色素类型仍然对 UVR 具有保护作用。
