Noncovalent binding of a mitomycin C metabolite, 2,7-diaminomitosene, to duplex DNA.
The major metabolite of mitomycin C, 2,7-diaminomitosene (DAM), interacts noncovalently with DNA. This was supported by ultraviolet-visible spectrum changes upon mixing with DNA and ethidium bromide displacement from DNA, measured as fluorescence changes. Moreover, DAM bound to DNA sufficiently strongly to hold DNA in a double stranded conformation under denaturing gel electrophoresis conditions commonly used to measure mitomycin C cross-links. These data show that generation of DAM and interaction with DNA represent a potential additional mechanism of DNA damage induced by mitomycin C.
Peterson
D M
DM
OncoPharmacia, Bozeman, MT 59715, USA.
Fisher
J
J
Beall
H D
HD
Ross
D
D
D000478:Alkylation; D000818:Animals; D001711:Biotransformation; D002417:Cattle; D003432:Cross-Linking Reagents / Q000378:metabolism; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D018736:DNA Adducts / Q000378:metabolism*; D004249:DNA Damage; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D006863:Hydrogen-Ion Concentration; D045563:Indolequinones; D007211:Indoles / Q000378:metabolism; D007364:Intercalating Agents / Q000378:metabolism; D016685:Mitomycin / Q000378:metabolism* / Q000494:pharmacology; D008937:Mitomycins / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D009690:Nucleic Acid Conformation / Q000187:drug effects; D009691:Nucleic Acid Denaturation; D010084:Oxidation-Reduction; D011809:Quinones / Q000378:metabolism
D003432:Cross-Linking Reagents; D018736:DNA Adducts; D045563:Indolequinones; D007211:Indoles; D007364:Intercalating Agents; D008937:Mitomycins; D011809:Quinones; C056417:mitomycin C-DNA adduct; C068040:quinone methide; D016685:Mitomycin; C056707:2,7-diaminomitosene; D004247:DNA; D016660:NAD(P)H Dehydrogenase (Quinone)