MULTIPLE FACTORS IN THE ETIOLOGY OF ORAL CANCER

口腔癌的一个重要病因是暴露于诱变剂; 该项目将分析单纯疱疹病毒的致突变活性， 1型病毒（HSV-1）。 HSV-L提高突变频率的方式 细胞将被检查。 病毒的功能 将被确定。 HSV-1将通过照射逐渐灭活 用紫外线来找出哪些病毒功能是必要的， 诱变 将筛选HSV-L DNA的克隆片段，以发现 基因组的某些区域负责提高突变频率。 特别是我们会发现宿主细胞关闭 病毒的功能及其致突变和恶性的机制 转型 病毒蛋白对细胞的影响可能会提高 将测试突变频率。 一种病毒蛋白MUT， 在目前的补助期内确定的，将予以审查， 与HSV-2的蛋白质HSO相比， 假设将被检验， MUT和HSO蛋白各自介导宿主细胞功能的关闭。 这两种蛋白质的基因将被克隆到表达载体中， 转染Vero细胞。 细胞的生长速率和稳定性 将测量细胞RNA。 将检测MUT和HSO的基因 以确定它们是否会将口腔上皮细胞转化为恶性表型。 如果转换获得，那么我们将定位网站上的 参与转化的蛋白质。 MUT和HSO蛋白 将对HSV-2进行表征。 两者的主要物理性质 将比较蛋白质以确定这两种蛋白质在功能上是否一致 相关. 该项目将导致一个详细的描述“击中和 HSV将细胞转化为恶性表型的“运行”机制。

An important etiological factor in oral cancer is exposure to mutagens; this project will analyze the mutagenic activity of the herpes simplex virus type-1 (HSV-1). The way in which HSV-L raises the mutation frequency of cells will be examined. The functions of the virus that are involved will be determined. HSV-1 will be progressively inactivated by irradiation with ultraviolet light to find which virus functions are necessary for mutagenesis. Cloned fragments of HSV-L DNA will be screened to find which regions of the genome are responsible for raising the mutation frequency. In particular we will find the relationship between the host cell shut-off function of the virus and the mechanisms of mutagenesis and malignant transformation. The effects on cells of viral proteins that might raise the mutation frequency will be tested. The role of a viral protein, MUT, that was identified in the present grant period will be examined and be compared with a protein, HSO, of HSV-2. The hypothesis will be tested that the MUT and HSO proteins each mediate the shut-off of host cell functions. The genes for the two proteins will be cloned in expression vectors and transfected into Vero cells. The growth rates of the cells and stability of cellular RNA will be measured. The genes for MUT and HSO will be tested to find if they transform oral epithelial cells to a malignant phenotype. If transformation is obtained, then we will locate the sites on the proteins that are involved in transformation. The MUT and HSO protein of HSV-2 will be characterized. The main physical properties of the two proteins will be compared to find if the two proteins are functionally related. The project will lead to a detailed description of the "hit and run" mechanism by which HSV transforms cells to a malignant phenotype.