MOLECULAR PATHOLOGY OF CARCINOGENIC DNA DAMAGE

DNA中光烷基化碱基修复的酶引发将是 调查过了。破坏这种DNA的内切酶活性将是 从人胎盘、培养的人细胞和微球菌中提纯 鲁特斯。我们将对这些酶进行表征。详细的物理和 将对基材进行化学分析，以确定准确的 酶识别的DNA畸形的类型。内切酶将是 通过测量受损的超螺旋DNA对NiCk的转化率来进行检测 形式。正常细胞的活性将与干皮病的活性进行比较。 遗传性色素沉着症、共济失调、延髓扩张症和Fanconi贫血 癌症发病率高的传染病。不足之处将是 通过包括酶在内的标准生化技术进行探索 净化。DNA的光烷基化导致烷基的加成 在嘌呤的8个碳上，与某些化学物质共有的变化 致癌物质。紫外线诱导的嘧啶二聚体对血管内皮细胞的影响 从培养的人类细胞DNA中切除尿嘧啶将是 调查过了。DNA中不可修复的损伤是诱变和致癌的。 因此，这些结果将有助于阐明肿瘤切除修复的机制。 正常细胞的DNA损伤与人类疾病的缺陷机制 这会导致癌症的发展。

The enzymic initiation of repair of photoalkylated bases in DNA will be investigated. An endonuclease activity that breaks such DNA will be purified from human placenta, cultured human cells and from Micrococcus luteus. These enzymes will be characterized. Detailed physical and chemical analysis of the substrate will be done to determine the precise type of DNA deformity recognized by the enzyme. The endonucleases will be assayed by measuring conversion of damaged superhelical DNA to the nicked form. The activity in normal cells will be compared to that in xeroderma pigmentosum, ataxia telangectasia and Fanconi's anemia, genetically transmitted diseases with high incidences of cancer. Deficiencies will be explored by standard biochemical techniques, including enzyme purification. Photoalkylation of DNA results in additions of alkyl groups at the 8-carbon of purines, an alteration shared with some chemical carcinogens. The effects of ultraviolet - induced pyrimidine dimers on excision of uracil from the DNA of cultured human cells will be investigated. Unrepaired damage in DNA is mutagenic and carcinogenic. Therefore these results will elucidate the mechanisms of excision-repair of DNA damage in normal cells and the defective mechanisms of human diseases that lead to the development of cancer.