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Biomarkers of Toxicity in Zebrafish
Citation:
Padilla, S. Biomarkers of Toxicity in Zebrafish. Edition 1, Chapter 5, Ramesh C. Gupta (ed.), Biomarkers in Toxicology. Elsevier Science Inc., Burlington, MA, , 103-112, (2014).
Impact/Purpose:
This is a review of the state of the literature on biomarkers of toxicity in the zebrafish.
Description:
Acknowledgements and Disclaimer: The author wishes to thank Drs. Robert MacPhail, William Mundy and Aimen Farraj for reviewing earlier versions of this manuscript. The author is also grateful to Deborah Hunter and John Havel for construction of the figures. This manuscript has been reviewed by the U.S. Environmental Protection Agency and approved for publication. Approval does not signify that the contents reflect the views of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. Introduction Given that zebrafish have now become an accepted model for toxicological studies in both the human health and ecological communities, this chapter takes stock of the status of biomarkers of toxicity that have been proposed for the zebrafish model. Most of what is discussed herein are biomarkers of effect, but the line between biomarkers of effect and exposure is often not well defined. Generally the chapter strives to present examples of many different types of biomarkers for many classes of toxicological ‘icities”, but the chapter should not be considered a comprehensive survey of all the zebrafish biomarker literature. Rather, it is a critical appraisal of the state of the effort to develop and identify biomarkers of toxicity in zebrafish. Zebrafish Background The zebrafish, a small (3-5 cm), freshwater teleost fish, not native to the Western Hemisphere (Spence et al, 2008), is a vertebrate species that is easy and inexpensive to rear and maintain in the laboratory. It is a model that is especially convenient for developmental studies because the offspring mature rapidly, with organogenesis complete by 3 days, and by 6 days the larva are free swimming and feeding. The overall body plan is much like other vertebrates and includes toxicologically relevant organ systems such as a liver with a large complement of cytochrome P450s (Goldstone et al, 2010; Otte et al, 2010; Stegeman et al, 2010; Tao & Peng, 2009; Weigt et al, 2011), a thyroid gland (Blanton & Specker, 2007; Porazzi et al, 2009; Walpita et al, 2009), and a blood-brain barrier (Eliceiri et al, 2011; Jeong et al, 2008). The model does, however, lack some other toxicologically relevant organs such as mammary glands, lungs, and prostate gland. Nevertheless, there are many examples where key developmental signaling pathways and their regulation are conserved between fish and mammals. A comparison of the mammalian and zebrafish genomes revealed long-range conserved synteny (i.e., “the maintenance of gene linkage on chromosomes of different species”; Kikuta et al, 2007), attesting to the similarity in important regulatory sequences and overall similarity in the genomes (Howe et al, 2013; Kikuta et al, 2007). Additionally, zebrafish have been reported to possess orthologs for 86% of the 1318 human drug targets tested (Gunnarsson et al, 2008). Due to the concordance between zebrafish and mammalian developmental pathways, the zebrafish model is often promoted for studying mammalian disease (reviewed in Penberthy et al, 2002; Shin & Fishman, 2002). For example, it has been suggested that zebrafish would be an excellent model for ocular disease (Gestri et al, 2012), ocular motor disorders (Maurer et al, 2011) , autism (Tropepe & Sive, 2003), and, in general, for the molecular dissection of developmental pathways (Dodd et al, 2000; Duggan et al, 2008; Fetcho, 2007; Gunnarsson et al, 2008; Ito et al, 2010; Spitsbergen & Kent, 2003; Xi et al, 2010; Xu & Zon, 2010). See Attachment