Roles Of Cyclooxygenase-1 & -2 In Uv-induced Skin Cancer

流行病学研究表明，紫外线（UV）辐射引起皮肤损伤，是非黑色素瘤皮肤癌发展的主要环境因素。研究了COX-1和COX-2缺乏以及COX-1和COX-2选择性抑制剂在高剂量急性紫外线诱导的皮肤损伤中的作用。结果表明，与野生型小鼠相比，缺乏COX-2而不缺乏COX-1的小鼠表现出剂量依赖性的表皮皮肤损伤和细胞死亡增加。与COX-1缺失或野生型小鼠相比，COX-2缺失小鼠的细胞凋亡水平增加了约2.5倍。COX-2缺失小鼠从急性紫外线诱导的表皮损伤中恢复的程度与COX-1缺失或野生型小鼠大致相同。然而，在与S Fischer博士正在进行的一项合作研究中，将COX基因型转移到无毛小鼠中，观察到COX-2缺乏导致慢性低紫外线剂量暴露小鼠皮肤肿瘤形成减少。目前正在研究这种高剂量急性效应与低剂量慢性效应的矛盾。

Epidemiological studies indicate that ultra violet (UV) radiation causes skin damage and is a major environmental agent in non-melanoma skin cancer development. The effects of COX-1 and COX-2 deficiency, as well as COX-1 and COX-2 selective inhibitors, in high dose acute UV induced skin damage have been studied. The results indicate that mice deficient in COX-2, but not COX-1, exhibit dose dependent increases in epidermal skin damage and cell death compared to wild type mice. Levels of apoptosis were increased about 2.5 -fold in COX-2 null mice compared to COX-1 null or wild type mice. The COX-2 null mice also recovered from the acute UV induced epidermal damage about the same as the COX-1 null or wild type mice. However, in an ongoing collaborative study with Dr. S Fischer using the COX genotype transferred into the hairless mouse, it has been observed that COX-2 deficiency causes reduced skin tumor formation in chronic low UV dose exposed mice. This paradox of high dose acute effects versus low dose chronic effects is now being investigated.