DNA strand scission by enzymatically reduced mitomycin C: evidence for participation of the hydroxyl radical in the DNA damage.
Phage DNA, as well as plasmid and mammalian DNA's, were exposed to a superoxide and hydroxyl radical-generating system containing NADPH-cytochrome P-450 reductase and mitomycin C, both with and without added Fe3+-ADP, in phosphate buffer at pH 7.5. The generation of superoxide (O2-.) and hydroxyl (.OH) radicals in the system was demonstrated by using ESR spectrometry with N-tert -butyl-alpha-phenylnitrone (PBN) as a spin trapping agent. Only the lambda DNA isolated after exposure to the O2-./.OH-generating system containing many lower molecular weight DNA fragments indicating DNA strand breaks. This breakage was completely inhibited by a .OH radical scavenger (sodium benzoate) and by catalase, but only slightly by superoxide dismutase. Thyroid and plasmid DNA's were both cleaved when exposed to the O2-./.OH-generating systems. It is suggested that the mechanism of DNA scission by mitomycin C described here closely resembles that induced by the anthracycline drugs.
Hamana
K
K
Kawada
K
K
Sugioka
K
K
Nakano
M
M
Tero-Kubota
S
S
Ikegami
Y
Y
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D010582:Bacteriophage lambda; D004247:DNA / Q000378:metabolism*; D004279:DNA, Viral / Q000378:metabolism; D005609:Free Radicals; D006878:Hydroxides / Q000378:metabolism; D017665:Hydroxyl Radical; D016685:Mitomycin; D008937:Mitomycins / Q000378:metabolism*; D010084:Oxidation-Reduction; D010957:Plasmids; D013552:Swine; D013961:Thyroid Gland
D000903:Antibiotics, Antineoplastic; D004279:DNA, Viral; D005609:Free Radicals; D006878:Hydroxides; D008937:Mitomycins; D017665:Hydroxyl Radical; D016685:Mitomycin; D004247:DNA