Chemical Education Today
Book & Media Reviews Molecular Toxicology P. David Josephy, with Bengt Mannervik and Paul Ortiz de Montellano. Oxford University Press: Oxford and New York, 1997. xv + 368 pp. ISBN 0-19-509340-2. $56.00.
This well-written book presents concepts of toxicology from a chemical, biochemical, and molecular biological perspective and serves as a welcome companion to other books on toxicology, which tend to have as a basis the characterization and quantification of toxic responses. This mechanistic approach should be particularly appealing to scientists with a strong chemical background. The book is an outgrowth of a course in molecular toxicology taught at the University of Guelph by the author, and it fills a much-needed niche as a textbook for a course focusing on biochemical mechanisms of toxicology. The clientele for such a course is advanced undergraduates or graduate students with a strong background in biochemistry, bioorganic chemistry, toxicology, or pharmacology. The book covers reactive intermediates and their interactions with nucleic acids, proteins, and lipids, the toxicology of molecular oxygen and oxidative stress being a particular highlight. In addition, the toxicology of aromatic amines, nitrosamines, polycyclic aromatic hydrocarbons, and chlorinated organic compounds is specifically addressed. After two introductory chapters that review some of the more important concepts in biochemistry and molecular biology, the next five chapters consider in detail biological oxidation and the toxicology of molecular oxygen. The oxygenmetabolite-detoxifying enzymes superoxide dismutase (SOD), catalase, and the peroxidases are discussed in separate chapters, as are the oxidative processes involving the respiratory burst, lipid peroxidation (written by Manfred Brauer and Phillipe Couture from the University of Guelph), and erythrocyte oxidative stress. These chapters are all written from the perspective of biochemical or chemical mechanism, with side bars on a variety of topics that add breadth to the presentation. As an example of this breadth, the chapter Superoxide and Superoxide Dismustases has sections on (i) the chemical and biological sources of superoxide, (ii) the forms, distribution, and assays of SOD (iii) genetic aspects of SOD, and (iv) mechanisms of superoxide toxicity and superoxide reactivity. Side bars in this chapter include discussions of the radiolysis of water, kinetics of SOD-catalyzed reactions, EPR spin trapping, and gene fusion. The chapters on catalase and the peroxidases, the respiratory burst, lipid peroxidation, and erythrocyte oxidative stress are less detailed, but they provide a framework for discussion of these topics that could easily be enhanced in a course setting. Chapter 9 is an introduction to xenobiotic metabolism and is a concise description of the important processes involved in modification of xenobiotics. These processes are considered in detail in Chapters 10 (Glucuronide Formation), 11 (Glutathione and Detoxification, written by Bengt Mannervik from the University of Uppsala), 12 (Arylamine N-Acyltransferase, written by Denis Grant from the Hospital for Sick Children, Toronto), 13 (Sulfotransferase), 14 544
(Cytochrome P-450, written by Paul Ortiz de Montellano from the UCSF), and 15 (The AH Receptor [that mediates the toxic response of p-dioxin], written by Patricia Harper from the Hospital for Sick Children, Toronto). These chapters are all excellent reviews of important topics, the cytochrome P-450 chapter being particularly detailed and informative. The last five chapters of the book focus on DNA modification and carcinogenesis. These sections detail the formation of modified DNA, how DNA adducts cause mutation in the genetic sequence, and how such mutagenesis may ultimately lead to carcinogenesis. Chapter 16 focuses on common DNA adduct formation and methods for the isolation and chemical characterization of small quantities of modified DNA isolated from cellular milieu. Identification of DNA adducts provides evidence for reactive intermediates and allows for elucidation of the mechanism of adduct formation. Chapter 17 reviews the basic types of mutations caused by DNA modifications such as chemical lesions and strand breaks, with a thorough consideration of enzymatic repair mechanisms for DNA damage, both before and after replication. Common mutagenicity assays, such as the lacI system and Ames assays, are discussed. Chapter 18 (written by Jean Jordan from the University of Ottawa) considers both oncogene activation and tumor suppressor gene inactivation as a consequence of mutation in these genes important in the initiation of carcinogenesis. The final two chapters offer a more detailed analysis of two classes of potent mutagens/carcinogens, Polycyclic Aromatic Hydrocarbons (Chapter 19) and Aromatic Amines (Chapter 20). These segments provide insight into the role of in vivo activation of these xenobiotics to ultimate carcinogens and their mode of action to produce DNA adducts and mutations, with Chapter 19 being a particularly thorough review of PAH chemistry. The book is well organized. The text is liberally augmented with chemical structures, reaction sequences, and graphical representations of protein structures and the like. At the end of each chapter is a list of notes providing entry to the primary literature. Referencing tends to be a bit uneven from chapter to chapter, probably because of the different authorships. In general, however, the notes do provide critical leading references or reviews for the reader seeking more depth in a topic. Of references, most are post-1980 some are very recent; others give reference to classic publications going back several decades. The book, then, will be of interest to a wide range of scientists, is an absolute necessity for every chemistry, biochemistry, or biosciences or medical center library, and will serve as a valuable supplement for both undergraduate and graduate courses in toxicology or as a text for a course designed around a mechanisms of toxicology format. Biochemists, toxicologists, and chemists will also want to have it at the ready on their bookshelves. Ned A. Porter Department of Chemistry Duke University Durham, NC 27708
Journal of Chemical Education • Vol. 75 No. 5 May 1998 • JChemEd.chem.wisc.edu
