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Chapter 14. Approaches for Evaluation of Mode of Action.
ABBOTT, B. D., A. WATKINS, C. R. WOOD, AND M. B. ROSEN. Chapter 14. Approaches for Evaluation of Mode of Action. 3rdChapter 14, Ron Hood (ed.), Developmental and Reproductive Toxicology. Informa Healthcare, London, Uk, , 429-444, (2012).
Cellular and molecular approaches vastly expand the possibilities for revealing the underlying mechanisms of developmental toxicity. The typical teratology screening test examines near-term fetuses after exposure throughout organogenesis and evaluates the potential for an exposure to disrupt development. The teratology assay can also provide insight regarding the organs and/or cellular processes that might be targeted. More specific information regarding the developmental stage(s) that are sensitive to disruption can be derived from dose-response studies where exposure is restricted to one or only a few days during development. Examination of the target organs or cells at these sensitive stages, particularly at early time points after exposure, can be important for identifying specific genes, proteins, and regulatory pathways that may be involved in the response. This chapter presents an overview of some of the morphological, cellular, and molecular techniques that are useful in studies of mode of action and provides examples of applications of each method for evaluation of embryonic responses to developmental toxicants. The techniques presented in this chapter may appear to be routine and straightforward. However, most or all of these methods can involve a considerable investment of effort, time, patience, and laboratory resources. This cautionary note is intended only to alert the investigator to the fact that these are not trivial undertakings. Even for experienced investigators, successful application of some of these techniques will not always be straightforward but may require intuitive adjustment of specific protocol conditions to suit the particular experimental situation. It is important to understand the principals and pitfalls of each technique. Although it is beyond the scope of this chapter to provide detailed methods and protocols, 'several sources of such information are cited. The internet is also a good resource for protocols and most of the major suppliers of reagents, kits, and supplies used in these methods provide general as well as specific protocols on their web sites. As each technique is discussed in this chapter, examples of applications in developmental biology and toxicology will be briefly described. These represent only a few of the many excellent studies that have used these methods and readers are encouraged to seek out other examples from the literature that are relevant to their particular interests.
This book chapter provides an overview of the methods available to researchers interested in evaluating the mode of action of developmental toxicants. This chapter will be of value to students, post doctoral fellows, and senior researchers who are exploring options for mechanistic studies. The Chapter provides basic information for well established techniques as well as newer molecular, genomic, and proteomic approaches and points out important advantages as well as limitations of each approach. Examples of applications to developmental toxicity studies are provided with cited literature and sources of additional information are listed (books and resources to be found on the intemet). This will be the Third Edition of the book and the earlier editions were well received by the scientific community
Record Details:Record Type: DOCUMENT (BOOK CHAPTER)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
TOXICOLOGY ASSESSMENT DIVISION
DEVELOPMENTAL TOXICOLOGY BRANCH