MULTIPLE FACTORS IN THE ETIOLOGY OF ORAL CANCER

口腔癌的一个重要致病因素是接触诱变剂； 这个项目将分析单纯疱疹病毒的诱变活性。 1型病毒(HSV-1)。单纯疱疹病毒L提高突变频率的途径 将对细胞进行检查。所涉及的病毒功能 将会被确定。单纯疱疹病毒1型将被辐射逐渐灭活 用紫外线找出哪些病毒功能是必需的 诱变。将对克隆的单纯疱疹病毒L DNA片段进行筛选，以找出 基因组的区域负责提高突变频率。 特别是，我们将发现宿主细胞关闭之间的关系 病毒的功能及其致突变和致癌机制 转型。可能升高的病毒蛋白对细胞的影响 将测试突变频率。病毒蛋白MUT的作用， 将审查在本授权期内确定的项目，并 与HSV-2的一种蛋白质HSO相比。这一假设将得到检验， MUT和HSO蛋白各自介导宿主细胞功能的关闭。 这两种蛋白的基因将被克隆到表达载体中并 转染入Vero细胞。细胞的生长速度和稳定性 细胞RNA的含量将会被测量。将测试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。 如果获得了转换，那么我们将在 参与转化的蛋白质。猪瘟病毒的MUT和HSO蛋白 HSV-2将被描述为。两种材料的主要物理性能 将对蛋白质进行比较，以找出这两种蛋白质是否具有功能 相关的。该项目将导致一个详细的描述，“命中和 HSV将细胞转化为恶性表型的“Run”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.