LIFE-SHORTENING EFFECTS OF ENVIRONMENTAL UV EXPOSURE

大气中保护性臭氧层的持续消耗可能 导致人体暴露在破坏性紫外线(UV)下的急剧增加 辐射。记录在案的紫外线照射对人体的不良影响包括 免疫抑制与皮肤肿瘤的发展。这些影响是 在小鼠身上也可以看到，这是研究中最常用的动物模型 紫外线效果。此外，长期暴露在紫外线辐射下会缩短 小鼠的寿命呈剂量依赖关系。这一发现表明 环境中紫外线暴露的增加也可能会减少人类的寿命。 在拟议的研究中，南美负鼠(Monodelphis Home Tica) 将被用来研究紫外线辐射的寿命缩短效应。 这种动物模型比实验室小鼠有一定的优势。 而人类和负鼠都有修复紫外线诱导的能力 高效切除修复和光复活的嘧啶二聚体(a 特定的光依赖酶途径)，小鼠完全缺乏 光复活能力和相对低效的切除 修理。此外，诱导光复活途径的能力 通过适当暴露在可见光下的负鼠允许相互关联 在紫外线照射的皮肤中形成嘧啶二聚体和 紫外线照射对健康的不利影响。这些负面影响是 被紫外线后阻止的光复活必须由紫外线诱导 二聚体，因为移除二聚体会阻止它们的发育。初步 对负鼠的研究表明，光复活可以减少 紫外线照射的急性皮肤反应的严重程度，减少了发病率 对长期暴露在紫外线下的动物的皮肤肿瘤，并减少一些 紫外线的免疫抑制作用。我们有初步证据表明 光复活治疗也部分地消除了寿命的缩短 负鼠长期紫外线暴露的影响。我们希望详细探讨一下 慢性紫外线暴露的寿命缩短效应。负鼠将被 暴露在缩短寿命的紫外线照射制度下；一半的动物 随后将暴露在光再激活光中。对于这些动物来说 对于只暴露在光激活光下的对照动物，寿命， 死因和免疫状态将会确定。比较 对这三组动物的研究结果将表明 紫外线照射的缩短寿命作用并将决定其作用 嘧啶二聚体的形成能延长寿命。

Continuing depletion of the protective ozone layer of the atmosphere may lead to dramatic increases in human exposure to damaging ultraviolet (UV) radiation. Documented adverse effects of UV exposure in man include immunosuppression and the development of skin tumors. These effects are also seen in the mouse, the most commonly employed animal model for studies of UV effects. In addition, chronic exposure to UV radiation shortens the lifespan of mice in a dose-dependent fashion. This finding suggests that increased environmental UV exposure may also decrease human longevity. In the proposed studies The South American opossum (Monodelphis domestica) will be used to investigate the life-shortening effects of UV radiation. This animal model offers certain advantages over the laboratory mouse. While both man and the opossum share the ability to repair UV-induced pyrimidine dimers by efficient excision repair and photoreactivation (a specific light-dependent enzymatic pathway), mice completely lack photoreactivation capabilities and have relatively inefficient excision repair. In addition, the ability to induce the photoreactivation pathway of the opossum by appropriate exposure to visible light allows correlations to be made between pyrimidine dimer formation in UV-exposed skin and adverse health effect of UV exposure. Those adverse effects which are prevented by post-UV photoreactivation must be initiated by UV-induced dimers, since removal of dimers prevents their development. Preliminary studies in the opossum demonstrate that photoreactivation lessens the severity of the acute skin response to UV exposure, decreases the incidence of skin tumors in animals chronically exposed to UV, and diminishes some immunosuppressive effects of UV. We have preliminary evidence that photoreactivating treatment also partially abrogates the life-shortening effect of chronic UV exposure in opossums. We wish to explore in detail the life-shortening effect of chronic UV exposure. Opossums will be exposed to a life-shortening UV irradiation regime; half of the animals will subsequently be exposed to photoreactivating light. For these animals and for control animals exposed only to photoreactivating light, lifespan, cause of death, and immune status will be determined. Comparison of results for these three groups of animals will indicate the mechanism of the life-shortening effect of UV irradiation and will determine the role of pyrimidine dimer formation in reducing lifespan.