MECHANISMS OF INDUCTION OF SKIN CANCERS BY UV LIGHT

阳光中存在的紫外线辐射(UV)是已知的 导致人类大多数皮肤癌的诱因。 因为皮肤癌是人类最常见的疾病 癌症方面，紫外线辐射是一种重要的环境致癌物。 该提案的基本目标是调查 紫外线致癌中的细胞癌基因。许多细胞癌基因 已知与各种人类和啮齿动物有关 肿瘤。用特定的化学物质诱发啮齿动物的肿瘤 导致特定癌基因的频繁激活。然而，它 目前尚不清楚紫外线辐射是否激活了人肝癌组织中的原癌基因 致癌物质专一性方式。因此，对紫外线的分析 诱发小鼠皮肤癌的活化癌基因和a 小鼠皮肤癌中癌基因激活的比较 相同的组织学类型，但由不同的化学物质诱导 致癌物质将允许对此进行实验评估 假设。如果紫外线诱发癌症的机制是 具体为化学致癌，然后分析 皮肤癌组织中存在可转化癌基因 在暴露在阳光下的身体部位进行的研究将揭示出同样的 癌基因在这些肿瘤中也被激活。我们建议 确定紫外线辐射是否会诱发小鼠皮肤癌 人类皮肤癌发生在暴露在阳光下的身体部位 含有相似的激活癌基因。致癌基因将是 通过它们诱导致瘤转化的能力来鉴定 DNA介导的基因转移到3个受体细胞系统 3T3、C3H10T1/2和人HOS细胞。鉴定出RAS癌基因 通过DNA转染法进行寡聚体探针分析 技术来确定它们的激活机制。如果非RAS 通过DNA转染法鉴定癌基因，我们将制作 尝试在噬菌体或粘粒载体中克隆该基因。 从这些研究中获得的信息可能有助于理解 肿瘤发生的分子机制，并可能提供一种 将这一信息应用于人类皮肤癌的方法。

Ultraviolet radiation (UV) present in sunlight is known to be responsible for the induction of most skin cancers in humans. Since cancers of the skin are the most prevalent form of human cancer, UV radiation is an important environmental carcinogen. The basic objective of the proposal is to investigate the role of cellular oncogenes in UV carcinogenesis. Many cellular oncogenes are known to be associated with a variety of human and rodent tumors. Induction of tumors in rodents by defined chemicals has resulted in frequent activation of specific oncogenes. However, it is not known whether UV radiation activates proto-oncogenes in a carcinogen-specific manner. Therefore, an analysis of UV- induced murine skin cancers for activated oncogenes and a comparison with the oncogenes activated in mouse skin cancers of the same histologic type but induced by different chemical carcinogens will permit experimental evaluation of this hypothesis. If the mechanism of UV-induction of cancer is as specific as chemical-induction of cancer, then an analysis of the presence of transfectable oncogenes in human skin cancers occurring on sun-exposed body sites will reveal whether the same oncogenes are also activated in these tumors. We propose to determine whether skin cancers induced in mice by UV radiation and human skin cancers occurring on sun-exposed body sites contain similar activated oncogenes. The oncogenes will be identified by their ability to induce tumorigenic transformation by DNA-mediated gene transfer into 3 recipient cell systems, NIH 3T3, C3H 10T1/2, and human HOS cells. Ras oncogenes identified by DNA transfection will be analyzed by the oligomer probe technique to determine their mechanism of activation. If non-ras oncogenes are identified by DNA transfection, we will make an attempt to clone the gene in a bacteriophage or cosmid vector. Information obtained from these studies may help to understand the molecular mechanisms of carcinogenesis and may provide a means of applying this information to human skin cancer.