STUDIES ON THE BONDING SPECIFICITY FOR MITOMYCIN C-DNA MONOALKYLATION PROCESSES

Information on the DNA-bonding and sequence specificity for mitomycin C (1a) and select derivatives under limiting reducing conditions has been gleaned by using the lambda-exonuclease stop assay and DNA restriction fragments. This procedure demonstrated that covalent modification of DNA by mitomycin C occurred preferentially at guanine residues within 5'CG and 5'GG sequences. The observed selectivity was shown to proceed at the monoalkylation state and was independent of the second (cross-linking) drug-bonding event. The bonding properties of mitomycin C have been compared with anthramycin, an antineoplastic agent of comparable size. The results of this investigation are discussed in light of findings previously reported for the bonding specificity of mitomycin C to DNA. Potential explanations are offered for the observed guanine specificity as well as the preference for 5'CG and 5'GG sequences within the duplex DNA.