Activation of aromatic amines by prostaglandin H synthase

Prostaglandin H synthase catalyzes the first step in the synthesis of prostaglandins from arachidonic acid. The peroxidase activity of this enzyme can support the oxidation of xenobiotics, particularly aromatic amines. This pathway of metabolism may contribute to the activation of carcinogenic aromatic amines in target tissues such as the skin, lung, and bladder. In this review, recent work on this subject is summarized. I emphasize the elucidation of the structures of aromatic amine oxidation products, and their interactions with biological macromolecules. Prostaglandin H synthase supports the activation of benzidine to a mutagenic species in the Ames (Salmonella typhimurium) test, and our studies of the mechanism of this activation are described.