DNA strand scission by iron complexes of meso-tetra(N-methylpyridyl)porphines.
The DNA strand scission activities of three positional isomers of Fe(III) meso-tetra(N-methylpyridyl)porphine (Fe(III)TnMPyP, where n = 2, 3 or 4) have been investigated using PM2 DNA as a substrate. A significant degree of strand scission activity was noted in the presence of oxygen without the addition of a reducing agent. This activity was probably due to the presence of reducing agents in the agarose gels used to separate the DNA forms, as higher levels were recorded with reducing agents added to the strand scission mixture. The relative order of strand scission activity in the absence of added reducing agents was found to be Fe(III)T2MPyP greater than Fe(III)T4MPyP greater than Fe(III)T3MPyP. Comparative studies were also made with Fe(II)bleomycin. High concentrations of some reducing agents inhibited strand scission. Oxygen was required to produce optimal strand scission activity for all three porphyrins. It was also noted from spectroscopic measurements that the reduced porphyrins were degraded in the presence of oxygen. Studies with a series of potential strand scission inhibitors suggest that hydrogen peroxide and possibly peroxy radicals are intermediates in the reaction mechanism, while diffusible hydroxyl radicals appear to be excluded. However, superoxide radicals cannot be ruled out.
Byrnes
R W
RW
Department of Biophysics, Roswell Park Memorial Institute, Buffalo, NY.
Fiel
R J
RJ
Datta-Gupta
N
N
D002374:Catalase / Q000494:pharmacology; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004229:Dithiothreitol; D005290:Ferric Compounds; D010084:Oxidation-Reduction; D010100:Oxygen / Q000633:toxicity; D011166:Porphyrins / Q000494:pharmacology*; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000494:pharmacology
D005290:Ferric Compounds; D011166:Porphyrins; D004247:DNA; D002374:Catalase; D013482:Superoxide Dismutase; D010100:Oxygen; D004229:Dithiothreitol