ADDUCTS OF MITOMYCIN C WITH NUCLEOTIDES

我们的第一个目标是确定几个共价加合物的结构 丝裂霉素C(MC)是一种临床上使用的抗肿瘤药物，由 脱氧鸟苷。我们最近从模型反应中分离出了这样的加合物 来自激活的MC与DNA的反应。结构研究 最近获得的假定的“交联型”加合物也被计划。 另一个目标是制定一项综合降级计划 MC修饰的DNA，然后进行高效液相分析，可以作为一种 不同DNA加合物的灵敏图谱分析。另一个目标是 该方法在体内或组织内MC修饰DNA中的应用 文化。预计这些研究将提供有关该模式的信息 MC的细胞毒性和抗肿瘤选择性的研究。从长远来看， 测试提供了一种方法来解决MC领域中的一般问题 修复、细胞毒性、致突变性、染色体改变等，导致 从分子水平上理解MC的这些生物学效应。

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.