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

环氧合酶 1 的作用

• 批准号: 7006565
• 负责人: Robert Langenbach
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7006565
• 关键词: apoptosis; biological signal transduction; cyclooxygenase inhibitors; cytoprotection; environment related neoplasm /cancer; environmental exposure; enzyme activity; enzyme deficiency; genetically modified animals; laboratory mouse; molecular oncology; prostaglandin endoperoxide synthase; prostaglandin receptor; protein kinase A; radiation related neoplasm /cancer; skin neoplasms; terminal nick end labeling; ultraviolet radiation

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.

流行病学研究表明，紫外线(UV)辐射会导致皮肤损伤，是非黑色素瘤皮肤癌发生的主要环境因素。研究了环氧合酶-1和环氧合酶-2缺乏以及环氧合酶-1和环氧合酶-2选择性抑制剂在大剂量急性紫外线皮肤损伤中的作用。结果表明，与野生型小鼠相比，COX-2基因缺陷小鼠的表皮皮肤损伤和细胞死亡呈剂量依赖性增加，而COX-1基因缺失的小鼠不表达COX-1基因。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基因缺失的小鼠也能从急性紫外线诱导的表皮损伤中恢复过来，与COX-1基因缺失或野生型小鼠大致相同。然而，在与S·费舍尔博士正在进行的一项使用COX基因转移到无毛小鼠的合作研究中，已经观察到COX-2缺乏会导致慢性低剂量紫外线照射小鼠皮肤肿瘤形成减少。这种高剂量急性效应与低剂量慢性效应的悖论现在正在调查中。