ADDUCTS OF MITOMYCIN C WITH NUCLEOTIDES

丝裂霉素 C 与核苷酸的加合物

• 批准号: 3168259
• 负责人: MARIA TOMASZ
• 金额: $ 13.05万
• 依托单位: HUNTER COLLEGE
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-07-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3168259
• 关键词: DNA; HeLa cells; X ray crystallography; alkylating agents; alkylation; antineoplastic antibiotics; circular dichroism; covalent bond; crosslink; deoxyguanosine; high performance liquid chromatography; human tissue; liver; mitomycin C; neoplasm /cancer pharmacology; nucleic acid sequence; nucleic acid structure; nucleosides; radiotracer; simian virus 40; tissue /cell culture; viral carcinogenesis

Our first aim is to determine the structure of several covalent adducts of mitomycin C (MC), a clinically used antitumor agent, formed with deoxyguanosine. We isolated such adducts recently from model reactions and from reactions of activated MC with DNA. Structural investigations of recently obtained putative "crosslink" type adducts are also planned. Another aim is development of a consolidated scheme of degradation of MC-modified DNA, followed by HPLC analysis, which can be used as a sensitive mapping assay of adducts from various DNAs. A further aim is application of this assay to DNA modified by MC in vivo or in tissue cultures. These studies are expected to provide information about the mode of cytotoxicity and antitumor selectivity of MC. In the long range, the assay offers a method to attack problems in general in the area of MC repair, cytotoxicity, mutagenicity, chromosomal alterations, etc., leading to understanding of these biological effects of MC in molecular terms.

我们的第一个目的是确定几个共价加合物的结构 丝霉素C（MC）是一种临床使用的抗肿瘤剂，由 脱氧鸟苷。 我们最近从模型反应和 来自活化的MC与DNA的反应。 结构调查 最近还计划了最近获得的推定的“交联”加合物。 另一个目的是制定合并的降级计划 MC修饰的DNA，然后进行HPLC分析，可以用作 来自各种DNA的加合物的敏感映射测定。 另一个目的是 将此测定法应用于MC在体内或组织中修饰的DNA 文化。 这些研究有望提供有关该模式的信息 MC的细胞毒性和抗肿瘤的选择性。 在远处 测定提供了一种在MC领域攻击问题的方法 修复，细胞毒性，诱变性，染色体改变等，领先 以分子术语了解MC的这些生物学作用。