转录因子核因子E2相关因子2对长期中波紫外线照射诱导皮肤肿瘤的影响

Effect of nuclear factor E2-related factor 2 on skin carcinoma induced by long-term midwave ultraviolet irradiation

背景:紫外线照射是引起皮肤肿瘤的重要环境因素,与其诱导氧化应激反应有关。核因子E2相关因子2是调节细胞内抗氧化应激反应的重要转录因子,胞浆蛋白Kelch样环氧氯丙烷相关蛋白1为其特异性受体,目前核因子E2相关因子2-胞浆蛋白Kelch样环氧氯丙烷相关蛋白1抗氧化系统与皮肤紫外线损伤的关系受到密切关注。目的:观察中波紫外线照射所致皮肤DNA氧化损伤及光致癌作用,研究转录因子核因子E2相关因子2对长期中波紫外线照射诱导小鼠皮肤肿瘤形成的影响。方法:取8周龄雌性核因子E2相关因子2基因敲除(Nrf2-/-)BALB/c小鼠和野生型(Nrf2+/+)BALB/c小鼠,以100mJ/cm2剂量的中波紫外线照射小鼠背部4h。另取Nrf2-/-小鼠和Nrf2+/+小鼠以300mJ/cm2剂量的中波紫外线对小鼠背部进行长期照射,每周3次,连续36周。结果与结论:Nrf2-/-小鼠表皮内8-羟基脱氧鸟嘌呤核苷阳性细胞数量显著高于Nrf2+/+小鼠(P<0.05),Nrf2-/-和Nrf2+/+小鼠中波紫外线长期照射诱导皮肤肿瘤数目和发生率接近(P>0.05),且皮肤肿瘤组织病理学改变相似,提示核因子E2相关因子2对急性中波紫外线照射所致的DNA损伤具有抗氧化防护作用,在长期中波紫外线照射致癌过程中,转录因子核因子E2相关因子2的活性可能受到多种因素的调节,其具体机制有待于进一步研究。

BACKGROUND： Ultraviolet irradiation is an important environmental factor causing skin tumor, which is associated with the induction of oxidatie stress reaction. Nuclear factor E2-related factor 2 （Nrf2） is a major transcription factor to adjust cellular antioxidant responses and Kelch-like ECH-associated protein 1 is the specific receptor, and the relation of Nrf2-Kelch-like ECH-associated protein 1 antioxidant system and skin ultraviolet damage is close recently. OBJECTIVE： To observe the DNA oxidative damage and photocarcinogenesis by ultraviolet irradiation on the skin of the mice, and to research the effect of Nrf2 transcription factor on skin carcinoma induced by long-term midwave ultraviolet irradiation. METHODS： Female 8-week-ofd Nrf2 gene-deficient （Nrf2/） BALB/c mice and age-matched female wild-type （Nrf2~/~） BALB/c mice were selected, then the midwave ultraviolet irradiation of 100 mJ/cm2 was given to the back of mice for 4 hours; ultraviolet irradiation of 300 mJ/cm2 was given to the back of mice three times a week for 36 weeks RESULTS AND CONCLUSION： The number of 8-hydroxy-2＇-deoxyguanosine positive in Nrf2-1- mice was significantly higher than that in Nrf2＋/＋mice （P 〈 0.05）. There was no significant difference between Nrf2/ and Nrf2＋/＋ mice in the mean number of tumors per animal and the incidence rate of tumors （P 〉 0.05）. The histopathology of skin tumors was similar in two groups. This result indicates that Nrf2 has antioxidant protective effect on acute ultraviolet irradiation-induced DNA oxidative damage, there may be various factors regulating the activity of Nrf2 transcription factor in chronic ultraviolet irradiation carcinogenic process, and it needs many further studies.