黑色素是一种自由基清除剂、抗氧化剂和广谱紫外线（UV）辐射吸收剂，能够保护皮肤免受环境致癌物质的侵害。然而，黑色素合成和受UV诱导的反应性黑色素物种也被认为与黑色素细胞基因毒性有关。在这里，我们使用了一种敏感于UVB的、NRAS突变小鼠模型TpN，试图调和黑色素的这些相互矛盾的功能。我们将一种Tyrosinase失活突变体杂合小鼠与C57BL/6J背景交叉，得到了白化和黑化小鼠。在哺乳后第三天，当皮肤角质细胞尚未被黑色素着色时，这些动物被暴露于单一的UVB剂量。约三分之一（35%）的黑色小鼠受到了保护，不会出现UVB加速的肿瘤形成。然而，黑色小鼠和白化小鼠的黑色素瘤生长速率、肿瘤突变负担和基因表达谱相似。白化小鼠的皮肤在照射后1小时内含有更多的环丙嘧啶二聚体（CPD）阳性细胞。然而，随着时间的推移，这种趋势逐渐反转，CPD在48小时后在黑色素细胞中变得更加明显。这些结果表明，在表皮色素缺乏的情况下，黑色素细胞黑色素能够减轻急性 UV 暴露的致瘤效应，但无法保护黑色素细胞免受 UVB 诱导的突变的损伤。© 2022 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.

Melanin is a free-radical scavenger, antioxidant, and broadband absorber of ultraviolet (UV) radiation which protects the skin from environmental carcinogenesis. However, melanin synthesis and UV-induced reactive melanin species are also implicated in melanocyte genotoxicity. Here, we attempted to reconcile these disparate functions of melanin using a UVB-sensitive, NRAS-mutant mouse model, TpN. We crossed TpN mice heterozygous for an inactivating mutation in Tyrosinase to produce albino and black littermates on a C57BL/6J background. These animals were then exposed to a single UVB dose on postnatal day three when keratinocytes in the skin have yet to be melanized. Approximately one-third (35%) of black mice were protected from UVB-accelerated tumor formation. However, melanoma growth rates, tumor mutational burdens, and gene expression profiles were similar in melanomas from black and albino mice. Skin from albino mice contained more cyclobutane pyrimidine dimer (CPD) positive cells than black mice 1-h post-irradiation. However, this trend gradually reversed over time with CPDs becoming more prominent in black than albino melanocytes at 48 h. These results show that in the absence of epidermal pigmentation, melanocytic melanin limits the tumorigenic effects of acute UV exposure but fails to protect melanocytes from UVB-induced mutagenesis.© 2022 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.