MECHANISMS OF INDUCTION OF SKIN CANCERS BY UV LIGHT

已知存在于阳光中的紫外线辐射（UV）是 是诱发人类大多数皮肤癌的罪魁祸首。 由于皮肤癌是人类最常见的癌症形式， 紫外线辐射是一种重要的环境致癌物质。 该提案的基本目标是调查 紫外线致癌作用中的细胞癌基因。 许多细胞癌基因 已知与多种人类和啮齿动物有关 肿瘤的 确定的化学物质在啮齿动物中诱导肿瘤， 导致特定致癌基因的频繁激活。 但 目前尚不清楚紫外线辐射是否会激活癌细胞中的原癌基因。 致癌物特异性方式。 因此，分析UV- 诱导小鼠皮肤癌的激活癌基因和 与小鼠皮肤癌中激活的癌基因相比， 相同组织学类型但由不同化学物质诱导 致癌物质将允许实验评估这一点 假说. 如果紫外线诱发癌症的机制是 特异性作为化学诱导癌症，然后分析 人皮肤癌中存在可转染癌基因 发生在暴露在阳光下的身体部位， 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在小鼠中诱发皮肤癌 和人体皮肤癌发生在暴露于阳光下的身体部位 含有类似的激活的致癌基因。 癌基因将 通过其诱导致瘤转化的能力鉴定， DNA介导的基因转移到3个受体细胞系统，NIH 3T3、C3H10T1/2和人HOS细胞。 ras癌基因鉴定 将通过寡聚体探针分析DNA转染 技术，以确定其激活机制。 如果非ras 通过DNA转染鉴定癌基因，我们将建立一个 尝试在噬菌体或粘粒载体中克隆基因。 从这些研究中获得的信息可能有助于理解 致癌的分子机制，并可能提供一个 将这些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.