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），一种临床上使用的抗肿瘤剂，由 脱氧鸟苷。 我们最近从模型反应中分离出这样的加合物， 来自活化的MC与DNA的反应。 结构研究 最近获得的推定的“交联”型加合物也在计划中。 另一个目标是制定一个统一的退化计划， MC修饰的DNA，然后进行HPLC分析，其可用作 来自各种DNA的加合物的灵敏作图测定。 另一目的是 本试验应用于体内或组织中MC修饰的DNA cultures. 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。 从长远来看， 分析提供了一种方法来解决问题，一般在该地区的MC 修复、细胞毒性、致突变性、染色体改变等，领导 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.