Sequence-specific DNA damage induced by reduced mitomycin C and 7-N-(p-hydroxyphenyl)mitomycin 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 bromide or actinomycin D before the addition of mitomycin C and the reducing agent. Fully reduced mitomycin C did not induce the DNA damage. The mitomycin C-inducing 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-(p-hydroxyphenyl)mitomycin C, which is reported to show a higher antitumor 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.
D010584:Bacteriophage phi X 174; D001483:Base Sequence; D001894:Borohydrides; D002614:Chelating Agents / Q000494:pharmacology; D004262:DNA Restriction Enzymes; D004279:DNA, Viral; D004229:Dithiothreitol; D007700:Kinetics; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology*; D010084:Oxidation-Reduction; D012965:Sodium Chloride / Q000494:pharmacology
D001894:Borohydrides; D002614:Chelating Agents; D004279:DNA, Viral; D008937:Mitomycins; D012965:Sodium Chloride; D016685:Mitomycin; C027281:7-N-(4-hydroxyphenyl)mitomycin C; C025364:sodium borohydride; D004262:DNA Restriction Enzymes; D004229:Dithiothreitol