Mechanism of formation of (deoxy)guanosine adducts derived from peroxidase-catalyzed oxidation of the carcinogenic nonaminoazo dye 1-phenylazo-2-hydroxynaphthalene (Sudan I).
We investigated peroxidase-mediated oxidation of and the formation of the (deoxy)guanosine adduct by 1-phenylazo-2-hydroxynaphthalene (Solvent Yellow 14, Sudan I), a liver and urinary bladder carcinogen for rodents and a potent contact allergen and sensitizer for humans. Using thin layer chromatography (TLC) and/or high performance liquid chromatography (HPLC) combined with mass and/or nuclear magnetic resonance (NMR) spectrometry, we characterized the structures of two major peroxidase-mediated Sudan I metabolites and those of the adducts of (deoxy)guanosine that are formed during Sudan I oxidation. Peroxidase oxidizes Sudan I to radical species that react with another Sudan I radical to form the Sudan I dimer, or in the presence of (deoxy)guanosine, the oxidized Sudan I can attack the exocyclic amino group of guanine, forming the 4-[(deoxy)guanosin-N(2)-yl]Sudan I adduct. The reaction product with a second Sudan I radical results in a dimer where the oxygen 2 radical of Sudan I reacted with carbon 1 in the second Sudan I skeleton. The Sudan I dimer is unstable and decomposes spontaneously to the second oxidation product. This compound consists of the 4-oxo-Sudan I skeleton connected via the oxygen of its 2-hydroxyl group and nitrogen of its azo group with carbon 1 of 2-oxonaphthalene, having a unique spironaphthooxadiazine structure. If (deoxy)guanosine is present during the formation of this Sudan I metabolite, an adduct, in which this Sudan I metabolite is bound to the exocyclic amino group of guanine, is generated. This (deoxy)guanosine adduct is again unstable and decomposes spontaneously to the same adduct that is formed by the direct reaction of oxidized Sudan I, the 4-[(deoxy)guanosin-N(2)-yl]Sudan I adduct. The results presented here are the first structural characterization of Sudan I-(deoxy)guanosine adducts formed during the oxidation of this carcinogen by peroxidase.
Dracínský
Martin
M
Institute of Organic Chemistry and Biochemistry, v.v.i., Academy of Sciences of the Czech Republic, Flemingovo n. 6, 166 10 Prague 6, Czech Republic.
Cvacka
Josef
J
Semanská
Marcela
M
Martínek
Václav
V
Frei
Eva
E
Stiborová
Marie
M
D055162:Biocatalysis; D002273:Carcinogens / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D004396:Coloring Agents / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D018736:DNA Adducts / Q000737:chemistry*; D003849:Deoxyguanosine / Q000737:chemistry* / Q000378:metabolism; D009284:Naphthols / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism*
D002273:Carcinogens; D004396:Coloring Agents; D018736:DNA Adducts; D009284:Naphthols; C024336:1-phenylazo-2-naphthol; D009195:Peroxidase; D003849:Deoxyguanosine