Scheme 1.
Formation of SA-Cys34 sulfenamide, sulfinamide, and sulfonamide adducts with N-oxidized metabolites of PhIP. The genotoxic metabolite HONH-PhIP undergoes oxidation to form Nitroso-PhIP, which forms a sulfinamide adduct, following rearrangement of the semimercaptal. HONH-PhIP forms reactive sulfate or acetate esters following conjugation reactions with phase II enzymes. These esters of HONH-PhIP react with SA to form the sulfenamide adduct at Cys34. The superoxide generated during the oxidation of HONH-PhIP to Nitroso-PhIP, or other reactive oxygen species (ROS), can convert the labile sulfenamide and sulfinamide adducts of SA-Cys34-PhIP to the stable sulfonamide linkage.