© 1990 Oxford University Press
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Mechanism of formation and 32P-postlabeling of DNA adducts derived from peroxidative activation of carcinogenic non-aminoazo dye 1-phenylazo-2-hydroxynaphthalene (Sudan I)
Department of Biochemistry, Faculty of Natural Sciences, Charles University 128 40 Prague, Czechoslovakia
1Institute of Toxicology and Chemotherapy, German Cancer Research Center 6900 Heidelberg, FRG
2Department of Molecular Biology, Research Institute for Tuberculosis and Respiratory Diseases 180 71 Prague, Czechoslovakia
Horseradish peroxidase in the presence of hydrogen peroxide mediates the activation of carcinogenic 1-phenyl-azo-2-hydroxynaphthalene (Sudan I) to DNA-bound products in vitro. The peroxidase activating system is > 10 times more effective with respect to DNA modification by Sudan I than the microsomal enzymes containing cytochrome P450. The DNA-binding reaction of the Sudan I metabolite(s) formed by the peroxidase system is dependent on Sudan I and H2O2 concentration and pH. Reactive intermediate(s) or product(s) of the Sudan I oxidation by peroxidase with a short half-life are responsible for the DNA modification. DNA modified by peroxidase-activated Sudan I becomes colored and has an absorption maximum at {small tilde} 480 nm. The modification of DNA by Sudan I metabolites(s) formed by the peroxidase system is inhibited by some compounds of physiological importance (ascorbate, glutathione, Mg2± ions) and by radical trapping agents (nitrosobenzene, methyl viologen). 32P-Postlabeling assay of the DNA modified by Sudan I activated by the peroxidase system indicates that the covalent DNA adduct formation is the principal type of the DNA modification. Four major and several minor adducts of deoxyribonucleotide 3',5'-bisphosphate from DNA with Sudan I metabolite(s) were detected by the classical Randerath 32P-postlabelling assay as well as by the nuclease P1 version of the same method.
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