PHOTODERMATOLOGICAL STUDIES

家养有袋Monodelphis代表了一种新的动物模型， 为了研究特定紫外线辐射(UVR)诱导的作用， 哺乳动物皮肤光生物学中的DNA损伤。和人类一样，体内的细胞 家蝇的表皮具有很高的摄食能力。 紫外线诱导的嘧啶二聚体的光复活(PR)。这 光依赖的修复途径的独特性质是只作用于 嘧啶二聚体和如果PR降低UVR诱导 光生物学反应是嘧啶二聚体的确凿证据 都参与了这一反应的诱导。相互关联的能力 紫外线诱导的分子损伤与皮肤的光生物反应 将为皮肤科领域提供有价值的信息， 尤其是那些涉及皮肤病理状况的区域。 该项目的长期目标是利用现有的公关能力 在有袋类动物的皮肤细胞中研究其作用和可能的作用部位， 紫外线诱导的嘧啶二聚体在哺乳动物光生物反应中的作用 皮肤。具体目标是：1)确定 真皮和表皮DNA中嘧啶二聚体的诱导。一个 这些作用谱中的一个与 光毒性反应的诱导将指示部位(皮肤 与表皮相比)；2)确定最佳 表皮DNA中嘧啶二聚体的光逆转条件 3)用PR法确定嘧啶二聚体在体内的作用。 紫外线照射对细胞周期动力学和组织病理学的影响 哺乳动物皮肤的变化；4)开展分裂治疗研究，其中 UVR暴露与PR处理之间的间隔时间延长 时间的流逝。光复活能力衰退的动力学 光毒反应的诱导可能预示着早期 在表达光毒事件时发生的反应。

The marsupial Monodelphis domestica represents a novel animal model with which to study the role of a specific ultraviolet radiation (UVR)-induced, DNA lesion in the photobiology of mammalian skin. As in humans, cells in the epidermis of M. domestica have a high capacity for the photoreactivation (PR) of UVR-induced pyrimidine dimers. This light-dependent, repair pathway has the unique property of acting only on pyrimidine dimers and if PR decreases the ability of UVR to induce a photobiological response it is definitive evidence that pyrimidine dimers are involved in the induction of that response. The ability to correlate UVR-induced molecular lesions with photobiological responses of the skin will contribute valuable information to the field of dermatology, especially those areas involved with pathological conditions of the skin. The long-term objective of this project is to use the PR capacity present in cells of marsupial skin to study the role, and possible site of action, of UVR-induced pyrimidine dimers in photobiological responses of mammalian skin. The specific aims are: 1) determine action spectra for the induction of pyrimidine dimers in dermal and in epidermal DNA. A concordance between one of these action spectra with an action spectrum for induction of phototoxic reactions will be indicative of the site (dermal vs. epidermal) of induction of phototoxicity; 2) determine optimal conditions for the photoreversal of pyrimidine dimers in the epidermal DNA of M. domestica; 3) use PR to determine the role of pyrimidine dimers in UVR-induced pertubations of cell cycle kinetics and histopathological changes in mammalian skin; 4) carry out split treatment studies in which the UVR exposure is separated from the PR treatment by increasing periods of time. The kinetics of the decay in the ability to photoreactivate the induction of a phototoxic reaction may be indicative of the kinds of early reactions that occur in the expression of phototoxic events.