Arachidonic Acid-Dependent Metabolism of Chemical Carcinogens and Toxicants

Abstract

Exposure to environmental chemicals is generally recognized as an important cause of human cancer (1). Investigations on the mechanisms responsible for the initiation of carcinogenesis by chemicals indicate that most chemicals must be metabolized to exert their carcinogenic effects. The central hypothesis underlying current thinking on the induction of cancer, as originally proposed by the Millers, is that chemical carcinogens are converted to electrophilic metabolites which covalently link to nucleophilic cellular macromolecules (2). DNA is considered the critical nucleophilic target associated with the induction of neoplasia (2). Studies on the metabolic activation of chemical carcinogens have focused primarily on two major classes of chemicals, the polycyclic aromatic hydrocarbons (PAH) and the aromatic amines. Prototypes of these two classes are benzo(a)pyrene, and 2-acetylaminofluorene or 2-naphthylamine, respectively.