Abstract
Aromatic amines are a class of environmental contaminants capable of producing a variety of toxic effects
including carcinogenesis and methemoglobinemia (1-6). These two end points are often effected by a common
metabolic intermediate, the TV-hydroxylamine. Carcinogenesis is thought to be initiated by the reaction of the
electrophilic IV-hydroxyamine or a conjugate thereof with DNA (4-6). In the red blood cell, the iV-hydroxylamine reacts with oxyhemoglobin through a process in which the oxygen bound to oxyhemoglobin oxidizes both reactants to produce methemoglobin and the arylnitroso interme- diate (1-3). The arylnitroso compound itself is a highly electrophilic species which reacts preferentially with thiols such as glutathione or the cysteine residues of proteins (7-12). Presumably, the thiols add to the nitrogen-oxygen double bond, sulfur attacking at nitrogen, to form a short-lived intermediate which either is reductively cleaved by other thiols to the hydroxylamine or stabilized by oxygen migration from the nitrogen to the sulfur atom to form a sulfinamide (7-10).