RELATIONSHIP BETWEEN DNA DAMAGE, MUTATIONS, AND CANCER

该研究旨在确定紫外线诱导的 DNA损伤和诱导突变的种类和位置， 癌 这些都是致癌作用的基本问题，因为 特定基因的突变显然在以下方面具有因果作用： 致癌作用，但这种分子机制， 突变的发生知之甚少。 例如，直接链接 致癌物诱导的DNA损伤和序列变化之间的关系还没有 但却是由内源基因产生的 研究将集中在 确定遗传损伤的序列位置，以及基因- HPRT中UV光产物的特异性和链特异性修复 基因和p53肿瘤抑制基因的人类细胞， 进行切除修复将获得HPRT突变体， 将对突变的HPRT基因进行测序。 的位置 突变将与基因损伤的位置进行比较， 最初和修复期后存在。 DNA的位置 皮肤（人类和小鼠）中p53基因的损伤将是相关的 在裸鼠皮肤中诱导的肿瘤中p53基因突变 通过UV。 这些数据将提供一个直接比较的种类和 紫外线诱导突变导致基因损伤的特定位置， 癌症，并将研究DNA修复在这一过程中的作用。

The research aims to determine the relationship between UV-induced DNA damage and the kinds and location of induced mutations and cancer. These are fundamental questions in carcinogenesis, since mutations in specific genes clearly have a causal role in carcinogenesis, yet the molecular mechanisms by which such mutations occur are poorly understood. For example, a direct link between carcinogen-induced DNA damage and sequence changes has not yet been made in an endogenous gene. The research will focus on determining the sequence location of genetic damage, and the gene- specific and strand-specific repair of UV photoproducts in the HPRT gene and the p53 tumor suppressor gene of human cells that differ in capacity for excision repair. HPRT mutants will be obtained and the mutated HPRT gene will be sequenced. The location of the mutations will be compared with the location of the gene damage present initially and after periods of repair. The location of DNA damage in the p53 gene in skin (human and mouse) will be correlated with mutations in the p53 gene in tumors induced in nude mice skin by UV. The data will provide a direct comparison of the kinds and specific location of gene damage with UV induced mutations and cancer, and will investigate the role of DNA repair in the process.