ADDUCTS OF MITOMYCIN C WITH NUCLEOTIDES

点击翻译按钮获取中文摘要

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.