Sánchez Ana G, Gabrielli Adriana, Keszenman Deborah J
Group of Biophysical Chemistry, Department of Biological Sciences, CENUR Litoral Norte, Universidad de la República, Rivera 1350, Salto, 50000 Uruguay.
Present Address: Citizen Science Program, Department of Biology, Bard College, 30 Campus Rd, Annandale-on-Hudson, NY 12504 USA.
Biophys Rev. 2025 Jan 28;17(2):537-545. doi: 10.1007/s12551-025-01275-0. eCollection 2025 Apr.
Solar radiation is predominantly Earth's natural ultraviolet (UV) radiation source. The biological effects of UV radiation have been the subject of scientific interest for decades. The most frequent and abundant types of DNA damage comprise the formation of cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone (6-4PP) photoproducts. Upon UVA excitation, the 6-4PPs may undergo an intramolecular 4 electrocyclization of the pyrimidone ring, arising photolesions known as Dewar isomers. The photochemistry pathways of UVA/UVB-induced DNA damage are discussed. Photosensitization-mediated reactions have traditionally been categorized as either oxygen-independent or oxygen-dependent. In oxygen-independent processes, the underlying mechanism involves triplet-triplet energy transfer. Among the reactive oxygen species (ROS) generated by UV radiation (O, O , OH, H₂O₂), singlet oxygen (O₂) is highly reactive and a primary contributor to oxidative DNA damage in cells and human skin following UVA exposure, as observed in the production of 8-oxoguanine (8-OxoG). The exposure of melanocytes to UV radiation upregulates nitric oxide synthase (NOS) and NADPH oxidase (NOX), producing nitric oxide and superoxide, which recombine to produce peroxynitrite. This highly oxidizing species is responsible for melanin chemiexcitation, producing carbonyl products that transfer energy to the DNA molecule to produce CPDs in the dark several hours after UV exposure ends. The peroxynitrite generated could also lead to other types of DNA damage, such as the formation of 8-nitroguanine (8-NitroG), which requires further study.
太阳辐射是地球主要的天然紫外线（UV）辐射源。几十年来，紫外线辐射的生物学效应一直是科学研究的热点。最常见且数量众多的DNA损伤类型包括环丁烷嘧啶二聚体（CPD）和嘧啶（6-4）嘧啶酮（6-4PP）光产物的形成。在UVA激发下，6-4PPs可能会发生嘧啶酮环的分子内4π电环化，产生称为杜瓦异构体的光损伤。本文讨论了UVA/UVB诱导的DNA损伤的光化学途径。传统上，光敏化介导的反应被分为氧非依赖型或氧依赖型。在氧非依赖型过程中，其潜在机制涉及三重态-三重态能量转移。在紫外线辐射产生的活性氧物种（ROS）（O、O₂、OH、H₂O₂）中，单线态氧（¹O₂）具有高度反应性，是UVA照射后细胞和人体皮肤中DNA氧化损伤的主要促成因素，如8-氧代鸟嘌呤（8-oxoG）的产生所示。黑素细胞暴露于紫外线辐射会上调一氧化氮合酶（NOS）和NADPH氧化酶（NOX），产生一氧化氮和超氧阴离子，它们重新结合产生过氧亚硝酸盐。这种强氧化性物质负责黑色素化学激发，产生羰基产物，这些产物在紫外线暴露结束数小时后在黑暗中向DNA分子传递能量以产生CPD。产生的过氧亚硝酸盐也可能导致其他类型的DNA损伤，如8-硝基鸟嘌呤（8-NitroG）的形成，这需要进一步研究。
