UVR-INDUCED MELANOCYTIC NEVI AND PROGRESSION TO MELANOMA

该项目的总体目标是进一步发展 实验室负鼠，Monodelphisdomesitica，作为一个独特的模式， 暴露于以下物质引起的黑素细胞皮肤损伤的研究 紫外线辐射（UVR）。 Monodelphis是唯一的哺乳动物 实验室物种，可用于实验检查 UVR暴露与黑色素瘤诱导和进展相关的事件 单独使用，没有化学增强剂的复杂因素， 发起人。 病因复杂且仅部分了解， 人类黑色素瘤发病率的增加，强调了 对这一严重威胁人类健康的问题进行进一步的生物医学研究。 我们已经使用了一种新的和有前途的方法紫外线引发黑色素瘤 在Monodelphis中，涉及新生儿（哺乳）阶段的暴露。 在这个项目中，我们的目标是建立紫外线辐射暴露的最佳条件 这将允许最经济的生产， 提供信息的病变。 我们打算描述临床和 从尿道起始病变到恶性病变的病理学进展 黑色素瘤，并确定核型变化的性质和程度 与转移性黑色素瘤相关， 他们 经过鉴定，建立了具有个体的系谱 高、低磁化率谱线。 使用适当的育种 策略，这些线然后可以用来调查遗传 调节黑色素瘤形成的多阶段过程， 来鉴定和描述相关基因。 该项目的一个重要组成部分是提供数据， 新生儿辐照研究中产生的动物或组织， 核心单位和其他项目。 用于检测的病变发生率数据 任何主要基因对易感性的影响将提供给核心 单位;将向项目3提供患有黑色素瘤的动物以进行疗效评估 候选化疗化合物的测试;以及来自 等位基因关联研究的受影响和未受影响个体， 候选肿瘤抑制基因和癌基因位点将提供给项目 6.

The overall objective of this project is to further develop the laboratory opossum, Monodelphis domesitica, as a unique model for investigations of melanocytic skin lesions induced by exposure to ultraviolet radiation (UVR) alone. Monodelphis is the only mammalian laboratory species that is available for experimental examination of the events associated with melanoma induction and progression by UVR exposure alone, without the complicating factors of chemical enhancers or promoters. The complex and only partially understood etiology, and the increasing incidence of human melanoma, underscore the importance of further biomedical research on this serious threat to human health. We have used a novel and promising method for UVR initiation of melanoma in Monodelphis which involves exposure at the neonate (suckling) stage. In this project we aim to establish optimal conditions for UVR exposure of neonates that will allow the most economical production of informative lesions. We intend to characterize the clinical and pathological progression of neonatally initiated lesions to malignant melanoma and to determine the nature and extent to karyotypic changes that are associated with metastatic melanomas and cell lines derived from them. After identification of pedigrees with individuals to establish high and low susceptibility lines. Using appropriate breeding strategies, these lines can then be used to investigate the genetic regulation of the multistage process of melanoma formation and ultimately to identify and characterize the genes involved. An important component of this project is to make available data, animals, or tissues arising from the neonate irradiation studies to the Core Unit and to other projects. Lesion incidence data for the detection of any major gene effect on susceptibility will be supplied to the Core Unit; animals with melanoma will be supplied to Project 3 for efficacy testing of candidate chemotherapeutic compounds; and tissues from affected and unaffected individuals for allelic association studies at candidate tumor suppressor and oncogene loci will be supplied to Project 6.