Halliday Gary M
Dermatology Research Laboratories, Division of Medicine, Melanoma and Skin Cancer Research Institute, Royal Prince Alfred Hospital at the University of Sydney, Sydney, NSW, Australia.
Mutat Res. 2005 Apr 1;571(1-2):107-20. doi: 10.1016/j.mrfmmm.2004.09.013.
Ultraviolet (UV) radiation causes inflammation, gene mutation and immunosuppression in the skin. These biological changes are responsible for photocarcinogenesis. UV radiation in sunlight is divided into two wavebands, UVB and UVA, both of which contribute to these biological changes, and therefore probably to skin cancer in humans and animal models. Oxidative damage caused by UV contributes to inflammation, gene mutation and immunosuppression. This article reviews evidence for the hypothesis that UV oxidative damage to these processes contributes to photocarcinogenesis. UVA makes a larger impact on oxidative stress in the skin than UVB by inducing reactive oxygen and nitrogen species which damage DNA, protein and lipids and which also lead to NAD+ depletion, and therefore energy loss from the cell. Lipid peroxidation induces prostaglandin production that in association with UV-induced nitric oxide production causes inflammation. Inflammation drives benign human solar keratosis (SK) to undergo malignant conversion into squamous cell carcinoma (SCC) probably because the inflammatory cells produce reactive oxygen species, thus increasing oxidative damage to DNA and the immune system. Reactive oxygen or nitrogen appears to cause the increase in mutational burden as SK progress into SCC in humans. UVA is particularly important in causing immunosuppression in both humans and mice, and UV lipid peroxidation induced prostaglandin production and UV activation of nitric oxide synthase is important mediators of this event. Other immunosuppressive events are likely to be initiated by UV oxidative stress. Antioxidants have also been shown to reduce photocarcinogenesis. While most of this evidence comes from studies in mice, there is supporting evidence in humans that UV-induced oxidative damage contributes to inflammation, gene mutation and immunosuppression. Available evidence implicates oxidative damage as an important contributor to sunlight-induced carcinogenesis in humans.
紫外线（UV）辐射可导致皮肤炎症、基因突变和免疫抑制。这些生物学变化是光致癌作用的原因。阳光中的紫外线辐射分为两个波段，UVB和UVA，两者都会导致这些生物学变化，因此可能导致人类和动物模型患皮肤癌。紫外线引起的氧化损伤会导致炎症、基因突变和免疫抑制。本文综述了以下假说的证据：紫外线对这些过程的氧化损伤会导致光致癌作用。UVA对皮肤氧化应激的影响比UVB更大，它会诱导活性氧和氮物种，这些物质会损伤DNA、蛋白质和脂质，还会导致NAD+消耗，从而使细胞能量损失。脂质过氧化会诱导前列腺素生成，与紫外线诱导的一氧化氮生成一起导致炎症。炎症促使人类良性日光性角化病（SK）恶性转化为鳞状细胞癌（SCC），可能是因为炎症细胞产生活性氧，从而增加了对DNA和免疫系统的氧化损伤。在人类中，随着SK进展为SCC，活性氧或氮似乎会导致突变负担增加。UVA在导致人类和小鼠免疫抑制方面尤为重要，紫外线脂质过氧化诱导的前列腺素生成和紫外线对一氧化氮合酶的激活是这一过程的重要介质。其他免疫抑制事件可能由紫外线氧化应激引发。抗氧化剂也已被证明可减少光致癌作用。虽然这些证据大多来自对小鼠的研究，但在人类中也有支持性证据表明紫外线诱导的氧化损伤会导致炎症、基因突变和免疫抑制。现有证据表明氧化损伤是人类阳光诱导致癌作用的重要促成因素。
