Mechanism of formation and 32P-postlabeling of DNA adducts derived from peroxidative activation of carcinogenic non-aminoazo dye 1-phenylazo-2-hydroxynaphthalene (Sudan I)
Language English Country England, Great Britain Media print
Document type Journal Article
- MeSH
- Autoradiography MeSH
- Benzoflavones pharmacology MeSH
- beta-Naphthoflavone MeSH
- Biotransformation MeSH
- DNA metabolism MeSH
- Rats, Inbred Strains MeSH
- Microsomes, Liver drug effects metabolism MeSH
- Carcinogens metabolism MeSH
- Kinetics MeSH
- Horseradish Peroxidase metabolism MeSH
- Rats MeSH
- Naphthols metabolism MeSH
- Phosphorus Radioisotopes MeSH
- Carbon Radioisotopes MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- 1-phenylazo-2-naphthol MeSH Browser
- Benzoflavones MeSH
- beta-Naphthoflavone MeSH
- DNA MeSH
- Carcinogens MeSH
- Horseradish Peroxidase MeSH
- Naphthols MeSH
- Phosphorus Radioisotopes MeSH
- Carbon Radioisotopes MeSH
Horseradish peroxidase in the presence of hydrogen peroxide mediates the activation of carcinogenic 1-phenylazo-2-hydroxynaphthalene (Sudan I) to DNA-bound products in vitro. The peroxidase activating system is greater than 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 approximately 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.
References provided by Crossref.org
Experimental approaches to evaluate activities of cytochromes P450 3A
