Al-Sadek Tarek, Yusuf Nabiha
Department of Dermatology, UAB Heersink School of Medicine, Birmingham, AL 35294, USA.
Curr Issues Mol Biol. 2024 Feb 29;46(3):1924-1942. doi: 10.3390/cimb46030126.
Ultraviolet (UV) radiation plays a crucial role in the development of melanoma and non-melanoma skin cancers. The types of UV radiation are differentiated by wavelength: UVA (315 to 400 nm), UVB (280 to 320 nm), and UVC (100 to 280 nm). UV radiation can cause direct DNA damage in the forms of cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs). In addition, UV radiation can also cause DNA damage indirectly through photosensitization reactions caused by reactive oxygen species (ROS), which manifest as 8-hydroxy-2'-deoxyguanine (8-OHdG). Both direct and indirect DNA damage can lead to mutations in genes that promote the development of skin cancers. The development of melanoma is largely influenced by the signaling of the melanocortin one receptor (MC1R), which plays an essential role in the synthesis of melanin in the skin. UV-induced mutations in the BRAF and NRAS genes are also significant risk factors in melanoma development. UV radiation plays a significant role in basal cell carcinoma (BCC) development by causing mutations in the Hedgehog (Hh) pathway, which dysregulates cell proliferation and survival. UV radiation can also induce the development of squamous cell carcinoma via mutations in the TP53 gene and upregulation of MMPs in the stroma layer of the skin.
紫外线(UV)辐射在黑色素瘤和非黑色素瘤皮肤癌的发生发展中起着关键作用。紫外线辐射的类型根据波长进行区分:UVA(315至400纳米)、UVB(280至320纳米)和UVC(100至280纳米)。紫外线辐射可导致环丁烷嘧啶二聚体(CPD)和6-4光产物(6-4PP)形式的直接DNA损伤。此外,紫外线辐射还可通过活性氧(ROS)引起的光敏反应间接导致DNA损伤,表现为8-羟基-2'-脱氧鸟嘌呤(8-OHdG)。直接和间接的DNA损伤均可导致促进皮肤癌发生发展的基因突变。黑色素瘤的发生在很大程度上受促黑素细胞激素1受体(MC1R)信号传导的影响,该受体在皮肤黑色素合成中起重要作用。BRAF和NRAS基因中的紫外线诱导突变也是黑色素瘤发生发展的重要危险因素。紫外线辐射通过导致Hedgehog(Hh)信号通路突变,在基底细胞癌(BCC)的发生发展中起重要作用,该突变会使细胞增殖和存活失调。紫外线辐射还可通过TP53基因突变和皮肤基质层中基质金属蛋白酶(MMP)的上调诱导鳞状细胞癌的发生。
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