MULTIPLE FACTORS IN THE ETIOLOGY OF ORAL CANCER

口腔癌与暴露于诸如 如烟草、酒精饮料和1型单纯疱疹病毒 (HSV-1)。然而，诱变的机制和An的作用 个体对这些病原体的易感性尚不清楚。我们 将进行实验，目的如下：第一，我们将 测试口服诱变剂导致特定的、有针对性的假设 人类细胞的突变。这将通过穿梭载体来完成 带有小的靶基因，将被引入培养的 细胞。突变将通过将穿梭载体暴露于 鼻烟提取物，对红葡萄酒中的诱变剂，由 用HSV-1感染细胞或通过感染 克隆了HSV-1 DNA片段。代理的组合将是 测试过。突变的穿梭载体将被恢复并 突变将通过对它们的DNA序列的测定来揭示。 这将显示突变是否位于一致的位置 在目标内，或在随机地点。它将显示是否 突变通常是相同类型或不同类型的。寄主 已经被重新排列并插入到目标中的DNA将被 进行了测序和鉴定。其次，我们将检验这一假设 口腔癌患者更容易患口腔癌 诱变剂多于对照受试者。淋巴细胞将从以下来源获得 口腔癌患者为对照组，并将 转化成淋巴母细胞系。他们将会是 用诱变穿梭载体转染，并暴露于 口服诱变剂可以单独使用，也可以混合使用。频率和频率 患者细胞中的突变类型将与 来自匹配的对照组受试者。这将显示单元格 口腔癌患者尤其容易患上一种 或者所有的口服诱变剂。它将显示诱变剂是否 在患者的细胞中产生不同类型的突变 与对照组相比。第三，我们将决定哪一种口述 单独或联合使用诱变剂，都可以将细胞转化为 恶性表型。将对特定的口服诱变剂进行检测 它们转化细胞的能力。仓鼠胚胎成纤维细胞将 暴露在诱变剂和特定的组合中 探员们。将计算变换的焦点的数量，并且 转化的细胞将通过接种进行致瘤性测试 变成仓鼠。这将显示哪些口服诱变剂是 可能单独致癌或与其他疾病合并致癌 探员们。

Cancer of the mouth is associated with exposure to mutagens such as tobacco, alcoholic beverages, and herpes simplex virus type-1 (HSV-1). However the mechanisms of mutagenesis and the role of an individual's susceptibility to these agents is not understood. We will perform experiments with the following aims: First we will test the hypothesis that oral mutagens cause specific, targeted mutations in human cells. This will be done with shuttle vectors with small target genes that will be introduced into cultured cells. Mutation will be induced by exposing the shuttle vector to extracts of snuff, to mutagens such as are in red wine, by infecting the cells with HSV-1 or by transfecting the cells with cloned fragments of HSV-1 DNA. Combinations of agents will be tested. The mutated shuttle vectors will be recovered and mutations will be revealed by determination of their DNA sequence. This will show whether the mutations are at a consistent site within the target, or at random sites. It will show whether mutations are usually of the same type or different types. Host DNA that has been rearranged and inserted into the target will be sequenced and identified. Secondly, we will test the hypothesis that patients with oral cancer are more susceptible to oral mutagens than control subjects. Lymphocytes will be obtained from patients with oral cancer an control subjects and will be transformed to lymnphoblastoid cell lines. They will be transfected with a mutagenesis shuttle vector and be exposed to the oral mutagens either singly or in combinations. The frequency and types of mutations in cell from patients will be compared with those from matched control subjects. This will show whether cells from patients with oral cancer are particularly susceptible to one or all of the oral mutagens. It will show whether the mutagens produce different types of mutation in cells form patients as compared with controls. Thirdly, we will determine which oral mutagens, alone or in combination, can transform cells to a malignant phenotype. Specific oral mutagens will be tested for their ability to transform cells. Hamster embryo fibroblasts will be exposed to the mutagenic agents and specific combinations of agents. The numbers of transformed foci will be counted and the transformed cells will be tested for tumorigenicity by inoculation into hamsters. This will show which of the oral mutagens are likely to be tumorigenic either alone or in combination with other agents.