title: Oxidations of the carcinogen N-hydroxy-N-(2-fluorenyl)acetamide by enzymatically or chemically generated oxidants of chloride and bromide.
abstract: The oxidations of the carcinogen N-hydroxy-N-(2-fluorenyl)acetamide (N-OH-2-FAA) via one-electron (1e-) oxidation to equimolar 2-nitrosofluorene (2-NOF) and N-acetoxy-2-FAA and via oxidative cleavage to 2-NOF by chemically and myeloperoxidase (MPO)/H2O2 generated oxidants of Cl- and/or Br- were investigated. 2-NOF was determined spectrophotometrically in the reaction mixtures and by HPLC of their extracts; N-acetoxy-2-FAA was determined by HPLC. In the presence of individual or mixed halides at their physiologic concentrations (0.1 M Cl- and/or 0.1 mM Br-) and pH 4-6, MPO/H2O2-catalyzed oxidation of N-OH-2-FAA to 2-NOF via oxidative cleavage was much greater than 1e- oxidation. At the respective pH optima, oxidation was much more rapid with Br- and Br- + Cl- than with Cl-. HOBr or HOCl + Br- oxidized N-OH-2-FAA more rapidly than HOCl, also chiefly via oxidative cleavage. This suggested that, in the presence of MPO/H2O2 + Cl- + Br-, oxidation was due to HOBr from HOCl oxidation of Br- and/or oxidation of Br- by MPO/H2O2. In the presence of taurine (1 or 10 mM), a scavenger of hypohalous acids, MPO/H2O2 catalysis of oxidative cleavage was unaffected with Br-, prevented with Cl-, and partially prevented with Cl- + Br-. These results were linked to N-halotaurine formation since it was found that N-bromotaurine, but not N-chlorotaurine, oxidized N-OH-2-FAA chiefly to 2-NOF. With time N-chlorotaurine and N-bromotaurine appeared to undergo a pH-dependent halide exchange with Br- and Cl-, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis.
authors.forename: C L
authors.initials: CL
authors.lastname: Ritter
authors.forename: D
authors.initials: D
authors.lastname: Malejka-Giganti
mesh_terms: D001965:Bromides / Q000737:chemistry*; D002712:Chlorides / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D006139:Guaiacol; D006863:Hydrogen-Ion Concentration; D006881:Hydroxyacetylaminofluorene / Q000737:chemistry*; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000032:analysis; D013056:Spectrophotometry, Ultraviolet; D013654:Taurine / Q000737:chemistry
chemical_list: D001965:Bromides; D002712:Chlorides; D013654:Taurine; D006881:Hydroxyacetylaminofluorene; D006139:Guaiacol; D009195:Peroxidase