Biological Reactive Intermediates

Book excerpt: The concept that detoxication is the inevitable result of biotransformation of xenobiotic compounds by mammalian systems has undergone modification since it was first described. Indeed, despite the fact that R. T. Williams popularized the notion, he was among the first to caution that it was not possible to predict the biological activities of the resulting metabolites. It has become increasingly apparent in recent years that not only do many metabolites of drugs and other chemicals display biological activity but also in many instances these metabolites play an important role in initiating several forms of cancer and are the cause of a variety of types of toxicity. Thus it seems appropriate to collect in one volume a series of reports outlining advances in the study of the formation of chemically active intermediary metabolic products of chemicals, mechanisms of toxicity or carcinogenesis, and pathways for true detoxication of these chemicals. The work of R. T. Williams, beginning in the late 1920s and early 1930s, marked the first concerted effort to understand the biotransformation of foreign chemicals in animals. He investigated the metabolic pathway of numerous compounds in a wide variety of animal species while training large numbers of our colleagues who have been responsible for further advances in biochemistry, pharmacology, and toxicology. Another pioneer in the study of drug metabo lism, B. B.