Sequeoce-spedfk Dna Damage Induced by Reduced Raitomydn C and 7-n-(p-hydroxy- Phenyl)mi(omydn C

Mitomycin C reduced with sodium borohydride Induced the DNA damage at deoxyguanosines preferentially in dinucleotide sequence G-T. The DNA damage produced strand breaks when subsequently heated. The DNA damage scarcely occurred when the end-labeled DNA was preincubated with ethidium brotmde or actinomycin D before the addition of mitomydn C and the reducing agent. Fully reduced mitomycin C did not induce the DNA damage. The mitomycin Cinducing DNA damage seems to require the intercalation of the partially reduced mitomycin C of short life time, probably semiquinone radical, between DNA base pairs. The inhibitory effects of sodium chloride and radical scavengers suggested that the requirement of the covalent bond formation of mitomycin C to DNA and the involvement of oxygen radicals in the DNA damage. 7-N-(£-hydroxyphenyl )mitomycin C, which is reported to show a higher antHumor activity and a lower toxicity than mitomycin C, was readily reduced with dithiothreitol and Induced the sequence-specific DNA damage, whereas mitomycin C was not.