RELATIONSHIP BETWEEN DNA DAMAGE, MUTATIONS, AND CANCER

这项研究旨在确定紫外线诱导的 DNA损伤和诱发突变的种类和位置 癌症。这些都是癌症发生中的基本问题，因为 特定基因的突变显然在 致癌的分子机制 人们对突变的发生知之甚少。例如，直接链接 致癌物诱导的DNA损伤和序列改变之间没有 但这是由一种内源性基因造成的。这项研究将集中在 确定遗传损伤的序列位置，并且该基因- HPRT中紫外光产物的特异性和单链特异性修复 人类细胞的抑癌基因与p53基因的不同 在切除修复能力方面。将获得HPRT突变体并 突变的HPRT基因将被测序。的位置。 突变将与基因损伤的位置进行比较 在最初和经过修理期后呈现。DNA的定位 皮肤(人和小鼠)中p53基因的损伤将是相关的 裸鼠皮肤诱发肿瘤中P53基因的突变 由紫外线照射。数据将提供种类和类型的直接比较 基因损伤的特定位置与紫外线诱导的突变和 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.