1995
DOI: 10.1021/bi00008a033 View full text |Buy / Rent full text
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Abstract: Mitomycin C (MC), mitomycin A, porfiromycin, BMY-25067, and BMY-25287, antitumor antibiotics collectively termed "mitosanes", were found to have no appreciable binding affinity to various natural and synthetic DNAs, as tested by UV spectrophotometry and equilibrium dialysis. Further tests of DNA binding applied to MC including thermal melting measurements, displacement of ethidium fluorescence, and unwinding of closed circular DNA were similarly negative. In contrast, 2,7-diaminomitosene (2,7-DAM), a major end… Show more

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“…In contrast to the low recovery of MC in the presence of MRD, drug recovery is high when MCRA is present in the reaction mixtures (23). Previously, it has been observed that unreduced MC does not appreciably bind to DNA (26). Consequently, failure to recover sufficient amounts of MC from the DNA protection reaction mixtures (Fig.…”
Section: Discussionmentioning
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rupbmjkragerfmgwileyiopcupepmcmbcthiemesagefrontiersapsiucrarxivemeralduhksmucshluniversity-of-gavle
“…In contrast to the low recovery of MC in the presence of MRD, drug recovery is high when MCRA is present in the reaction mixtures (23). Previously, it has been observed that unreduced MC does not appreciably bind to DNA (26). Consequently, failure to recover sufficient amounts of MC from the DNA protection reaction mixtures (Fig.…”
Section: Discussionmentioning
“…The benefit of preventing reduction of the drug includes the inhibition of the precovalent recognition of DNA (26) by the reactive quinone methide and the suppression of oxygen radical formation due to redox cycling of the MC semiquinone radical (32). Continued biochemical characterization of the MC-MRD complex may provide further insight into the mechanism of this important class of antitumor compounds.…”
Section: Discussionmentioning
“…The viscosity of the RNA-dye complex was determined by measuring the time taken for the solution to flow through a Cannon-Manning semi micro size 75 capillary viscometer (Cannon Instruments Company, State College, PA, USA) that was submerged in a thermostated bath maintained at 20 ± 1°C as reported previously [36,40,44].…”
Section: Viscometric Studiesmentioning
“…The relative increase in length, L/L 0 , can be obtained from a corresponding increase in relative viscosity using the following equation [36,44].…”
Section: Viscometric Studiesmentioning
“…The partitioning of the active form of MC into reaction with DNA versus conversion to inactive metabolites depends on the kinetic competition of the two processes [9]. In contrast to most natural products, which interact with DNA, MC has no DNA-binding affinity until after its conversion to activated mitosene forms [10]. Therefore, it is likely that much of the MC that enters the cell is activated at intracellular locations, which are not in the vicinity of DNA.…”
Section: Introductionmentioning