DNA REPAIR AFTER POLYCYCLIC HYDROCARBON ADMINISTRATION

多环烃施用后的 DNA 修复

• 批准号: 3174254
• 负责人: EDWARD BRESNICK
• 金额: $ 12.42万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-05-01 至 1989-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3174254
• 关键词: DNA methylation; DNA repair; alkylating agents; asbestos; benzanthracenes; benzopyrenes; carbopolycyclic compound; chemical carcinogenesis; enzyme mechanism; gel electrophoresis; gel filtration chromatography; hamsters; high performance liquid chromatography; laboratory mouse; laboratory rat; methylnitrosourea; newborn animals; nutrition related neoplasm /cancer; nutrition related tag; pathogenic diet; radiotracer; respiratory epithelium; squamous cell carcinoma; trachea; tritium; vitamin A deficiency

A major hypothesis in chemical carcinogenesis is that an interaction between the chemical and cellular is a prerequisite for transformation. Cells generally possess DNA repair pathways for at least some of the resulting damage. The absence or deficiency of a repair process may predispose to cancer. This research will investigate the repair of two types of DNA damage, that induced by either benzo(a)-pyrene or methylnitrosourea; in the latter case, repair of a specific lesion, 0/6-methylguanine. Previous experiments with hamster tracheal epithelial cells suggest that benzo(a)pyrene adducts in DNA are repaired by a pathway that differs from ultraviolet light-induced pyrimidine dimers. This will be confirmed by purification of the enzymes involved. Furthermore, DNA repair-deficient cells will be isolated and used both for comparison of the different repair mechanisms, as well as for experiments to isolate the repair genes. With regard to repair of 0/6-methylguanine, we have already transfected DNA from human liver into repair-deficient Chinese hamster ovary cells and selected a clone that expresses the methyltransferase gene. The gene will now be isolated from these cells and used to obtain information on the mRNA and protein structure. Antibodies to the protein, will be obtained using, as immunogen, either the purified protein or a synthetic polypeptide, the sequence of which can be obtained directly from the DNA sequence. The antibodies and genetic probes will be used to assess variations within the human population.

化学癌发生的主要假设是相互作用 化学和细胞之间是转化的先决条件。 细胞通常具有至少一些的DNA修复途径 导致损坏。 维修过程的缺失或缺乏可能 易感癌症。 这项研究将调查两个的维修 DNA损伤的类型，由苯并（a） - 吡啶或 甲硝基在后一种情况下，修复特定病变， 0/6-甲基鸟嘌呤。 先前使用仓鼠气管上皮的实验 细胞表明DNA中的苯并（a）pyrene加合物通过途径修复 这与紫外线诱导的嘧啶二聚体不同。 这会 通过纯化所涉及的酶确认。 此外，DNA 修复缺陷的细胞将被隔离，并用于比较 不同的维修机制以及用于分离的实验 修复基因。 关于维修0/6-甲基鸟嘌呤，我们已经 从人肝脏转染的DNA到维修缺陷的中国仓鼠 卵巢细胞并选择一种表达甲基转移酶的克隆 基因。 现在，该基因将从这些细胞中分离出来，并用于获得 有关mRNA和蛋白质结构的信息。 蛋白质的抗体， 将以免疫原为纯化蛋白或A 合成多肽，可以直接从中获得的序列 DNA序列。 抗体和遗传探针将用于评估 人口中的变化。