PHOTODERMATOLOGICAL STUDIES

有袋动物Monodelphis arctica代表了一种新的动物模型， 其中研究了特定紫外线辐射（UVR）诱导的作用， 哺乳动物皮肤光生物学中的DNA损伤。 与人类一样， M.南极洲有一个高容量的 UV诱导的嘧啶二聚体的光复活（PR）。 这 光依赖性修复途径具有仅作用于 嘧啶二聚体，如果PR降低UVR诱导细胞凋亡的能力， 光生物学反应，这是明确的证据，嘧啶二聚体 参与了这种反应的诱导。 将人类的行为 紫外线辐射引起的皮肤光生物学反应的分子损伤 将为皮肤病学领域提供有价值的信息， 特别是涉及皮肤病理状况的那些区域。 这个项目的长期目标是利用现有的公关能力 在有袋类动物皮肤的细胞中研究其作用，以及可能的作用部位， 紫外线诱导的嘧啶二聚体在哺乳动物光生物学反应中的作用 皮肤 具体目的是：1）确定 在真皮和表皮DNA中诱导嘧啶二聚体。 一 这些作用谱之一与以下作用谱之间的一致性 光毒性反应的诱导将指示该部位（皮肤 vs.表皮）诱导光毒性; 2）确定最佳 表皮DNA中嘧啶二聚体的光逆转条件 分枝3）使用PR来确定嘧啶二聚体在 UVR诱导的细胞周期动力学和组织病理学紊乱 哺乳动物皮肤的变化; 4）进行分割治疗研究， UVR暴露与PR处理通过增加时间间隔分开 时间了 光活化的能力衰减的动力学 光毒性反应的诱导可以指示早期的 光毒性事件表达中发生的反应。

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.