Abstract
Since the foundation for Receptor Theory was laid a hundred years ago, biologists have used the theory to advance their disciplines and explain the perplexing questions that have emerged. It should be no surprise that Receptor Theory would find its way into toxicology. In the case of the aryl hydrocarbon receptor (AHR), important information began to emerge just in the last 35 years, but in that time frame, the advances have been rapid and many. The editor of The AH Receptor in Biology and Toxicology recognized the need to give organization and order to a rapidly growing body of knowledge that was poised to become unintelligible. The book provides clarity for a researcher who is new to the field as well as for those researchers who have, in the past, contributed to the understanding of the AHR. However, the greatest and lasting value of the book lies in pointing out the connection between Receptor Theory and toxicology testifying that toxicology is an independent medical science just like pharmacology, biochemistry and physiology.
The 533-page book is divided into 4 parts that contain 35 chapters. The first part, which contains only 1 chapter, constitutes 6% of the book but sets the stage of the text by laying out the historical background of AHR. The chapter has limited but succinct prose that is supported with over 400 references.
Part II, “AHR as a Ligand-Activated Transcription Factor,” contains 10 chapters and constitutes 28% of the book. The initial chapter in this section gives an overview of the AHR functional domains, signaling pathways, and induction of the drug-metabolizing enzymes. The remaining chapters cover, in great detail, topics such as chaperone proteins, AHR-specific ligands, gene expression and regulation of AHR, interaction of the AHR with other receptors, and genes associated with AHR expression. The section concludes with a chapter on the epigenetic influences that govern the AHR function.
Part III, “AHR as a Mediator of Xenobiotic Toxicities: Dioxins as a Key Example,” ties the ligand properties of AHR to the manifestation of toxicity. Part III constitutes 39% of the book and is likely the part that most toxicologists, who are not actively engaged in AHR research, would have an interest. The 15 chapters that make up part III cover, with a toxicological focus, topics such as hepatic transcription, oxidative stress mechanisms, cancer, regulation of immunotoxicity, AHR-mediated teratogenesis, and developmental toxicity. Several chapters at the end of part III are distinctly practical for the practicing toxicologist. These application-oriented chapters cover topics such as AHR impacts on teeth and bone, AHR signaling in wildlife, adverse human health outcomes, applications of AHR-dioxin toxicity in risk assessments, and other nondioxin ligands that activate the AHR from dietary sources. The final chapter of part III describes transgenic mice as an animal model for human exposure to AHR ligands.
Part IV, the final part, contains 9 chapters comprising 25% of the book and is entitled “AHR as a Physiological Regulator.” Part IV is the justification of the word “Biology” in the book’s title. The initial chapter in the fourth part, “Structural and Functional Diversification of AHRs During Metazoan Evolution,” documents the diversity and ubiquitous nature of AHRs through complex living organisms. Subsequent chapters speak the role of AHR in cardiac function and regulation, the development of liver and blood vessels, the development of both female and male reproductive systems, the control of cell cycle and apoptosis, cell adhesion and migration, immune system physiology, and the molecular control of circadian rhythms.
One could argue that the book is short on a teleological discussion of the AHR, but would most toxicologists find such a discussion beneficial? The original or evolutionary purpose of the AHR in most toxicologists’ minds is trumped by the consequences of AHR functions and AHR’s relationship to xenobiotics, even though the original purpose of the AHR may be a response to the herbivorous nature of animals. 1 Toxicologists interested in toxins from plant sources, or more pointedly botanical and dietary supplement products, recognize or should recognize that the AHR is more than a polycyclic aromatic hydrocarbon receptor and understand AHR’s role in absorption and metabolism of dietary phytochemicals. Furthermore, the role of AHR to herbivorous dietary traits of animals is beyond the scope of the book.
There are 4 pages of 14 color plates, labeled as “Figures,” nested between chapters 17 and 18. These color plates complement visual diagrams in 7 of the chapters. The color plates duplicate the figures that are contained within the chapters and thankfully so. The figures embedded within the chapters are difficult to read and understand because of their complexity; however, the color versions, which in many cases are larger, give the deserving and necessary clarity to the story that is told in the text. Because there is notation in the legend of the black and white figures within the chapter that a color plate exists of the same figure, the reader has the best of both worlds: a black and white version of the graphic at hand while reading and a color plate to study the concepts from the written text with more intensity—a true gift from the editor or publisher or both!
Theories that unify apparently disjointed, contradictory, or unrelated observations create interest and result in a flurry of activity and investigations. Newly formulated theories provide launching pads for forays and wholesale raids into Mother Nature’s collection of secrets. There is no better example than Receptor Theory to see biologic epistemology in action. There is no better example than the AHR to show that toxicology is an integral part of biology, medicine, and health, and The AH Receptor in Biology and Toxicology serves as its testament. Thanks to the Editor and the 75 chapters’ authors, toxicologists can cite a single source connecting specialized adverse responses with Receptor Theory.
The AHR researchers, toxicologists or not, would benefit from the presence of the book at their elbow. Life scientists, toxicologists or not, searching for new areas to explore will find a treasure trove of ideas in the book. General toxicologists might find the book too specialized for their interests, but if they would ever need a historical perspective of the AHR, then the 1st chapter of 29 pages would meet that need and is worth the purchase price of the book.
Publishers who wish to submit books to be reviewed should send their request for review along with the books directly to book review editor. Occasionally, books and monographs are published and reach the scientific community before publishers send courtesy copies to IJT for consideration as a text to be reviewed. If a reader would like a book or monograph reviewed or would like to submit a review to be considered for publication in IJT, please submit your book, suggestion or manuscript to:
Robert W. Kapp Jr., PhD,
Fellow ATS
Book Review Editor
International Journal of Toxicology
BioTox
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