Yarosh D, Alas L G, Yee V, Oberyszyn A, Kibitel J T, Mitchell D, Rosenstein R, Spinowitz A, Citron M
Applied Genetics Inc., Freeport, New York 11520.
Cancer Res. 1992 Aug 1;52(15):4227-31.
UV exposure has been linked to skin cancer in humans by epidemiology and the rare genetic disease xeroderma pigmentosum. However, UV produces multiple photoproducts in DNA, and their relative contribution is uncertain. An enzyme which specifically repairs cyclobutane pyrimidine dimers in DNA, T4 endonuclease V, was encapsulated in liposomes for topical delivery into mouse and human skin. In both species, liposomes applied after UV exposure localized in the epidermis and stimulated the removal of cyclobutane pyrimidine dimers. UV-irradiated mice treated with these liposomes had a dose-dependent decrease in the incidence of squamous cell carcinoma compared to controls. The results demonstrate that unrepaired cyclobutane pyrimidine dimers in DNA are a direct cause of cancer in mammalian skin.
通过流行病学以及罕见的遗传性疾病色素性干皮病，紫外线暴露已被证明与人类皮肤癌有关。然而，紫外线会在DNA中产生多种光产物，它们的相对作用尚不确定。一种能特异性修复DNA中环丁烷嘧啶二聚体的酶——T4内切核酸酶V，被包裹在脂质体中，用于局部递送进小鼠和人类皮肤。在这两个物种中，紫外线照射后应用的脂质体定位于表皮，并刺激了环丁烷嘧啶二聚体的去除。与对照组相比，用这些脂质体处理的紫外线照射小鼠鳞状细胞癌的发病率呈剂量依赖性降低。结果表明，DNA中未修复的环丁烷嘧啶二聚体是哺乳动物皮肤癌的直接原因。
