LIFE-SHORTENING EFFECTS OF ENVIRONMENTAL UV EXPOSURE

保护性的大气臭氧层的持续消耗可能 导致人类暴露于有害紫外线（UV）的急剧增加 辐射 紫外线照射对人体的不良影响包括 免疫抑制和皮肤肿瘤的发展。 这些影响是 也见于小鼠，最常用的动物模型的研究 紫外线的影响。 此外，长期暴露于紫外线辐射会缩短 以剂量依赖性方式延长小鼠的寿命。 这一发现表明 环境紫外线暴露的增加也可能减少人类寿命。 在拟议的研究中，南美洲负鼠（Monodelphis arctica） 将用于研究紫外线辐射对寿命缩短的影响。 这种动物模型比实验室小鼠具有某些优势。 虽然人类和负鼠都有修复紫外线引起的 嘧啶二聚体通过有效的切除修复和光复活（a 特异性光依赖性酶途径），小鼠完全缺乏 光复活能力，切除效率相对较低 修复. 此外，诱导光复活途径的能力 负鼠通过适当的暴露在可见光下， 在紫外线暴露的皮肤中形成嘧啶二聚体和 紫外线照射对健康的不良影响。 这些不利影响， 防止后UV光复活必须启动UV诱导的 二聚体，因为去除二聚体会阻止它们的发展。 初步 对负鼠的研究表明， 严重程度的急性皮肤反应紫外线照射，降低发病率 皮肤肿瘤的动物长期暴露于紫外线，并减少一些 UV的免疫抑制作用。 我们有初步证据表明 光活化处理也部分消除了寿命缩短 慢性紫外线暴露对负鼠的影响。 我们希望详细探讨 长期暴露在紫外线下会缩短寿命 负鼠将会 暴露于缩短寿命的紫外线照射制度;一半的动物 随后将暴露于光活化光。 为这些动物 而对于仅暴露于光活化光的对照动物，寿命， 死亡原因和免疫状态将被确定。 比较 这三组动物的结果将表明 紫外线照射的寿命缩短效应，并将决定 嘧啶二聚体形成减少寿命。

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.