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An Environmental Toxicogenomic Approach to Small Aquarium Fish Models.
FY 2003 Abstract (Year 1)
In this proposal, scientists from The University of Southern Mississippi (USM) and Southwest Texas State University (SWT) will collaboratively exploit recently developed microarray technology to build a toxicogenomic database for application in model small laboratory fish species. An overall aim of these studies is to delineate specific genetic changes reflective of exposures to adverse environmental conditions. The proposed program will build on collective expertise in molecular genetics and toxicology, aquatic animal stock maintenance, refined exposure methodologies and toxicological response assessments. Ultimately, the data acquired and the models developed will be used to assess and monitor responses of both laboratory and feral fishes to environmental perturbations. This information will assist federal agencies in assessment of the health of fish stocks and the effects of anthropogenic inputs and will add fundamental knowledge on the genomic effects of environmental toxicants.
Initially, this project will apply oligonucleotide microarray technology to two aquaria fish model systems; medaka (Oryzias latipes) and platyfish/swordtails (Xiphophorus). Each has unique attributes that make its use valuable for comparing responses between those two species, with those of other fish models and with those of animal models in general. Data derived from our application of microarray technologies to these aquaria models will be valuable for assessment of feral fish health and effects of individual toxicants in laboratory exposures and as bio-indicators of environmental exposure to genotoxic agents. Development and application of microarray technologies in these systems will have significant and substantial scientific fallout.
A toxicogenomics approach to risk assessment will be pursued, in which RNA extracted from model fish species that have been exposed to various types and ranges of hazardous chemicals is assessed for modulated patterns in gene expression using to be developed microarrays. Dose response curves acquired using long-term traditional biological endpoints (whole animal toxicity) will be included in our development of this toxicogenomics approach. Transcriptional profiling at each point along a dose response curve will assess multi-target gene regulatory circuits indicating selective responses to specific levels of environmental agent. In the long term, genetic profiles to be developed may be utilized to monitor reservoirs and other water systems as an additional indicator of system health and these data compared with currently employed risk assessment methods.
The proposed studies are expected to enhance scientific knowledge regarding molecular mechanisms of toxicity and cellular defense and recovery processes in vertebrates. Furthermore, we expect that these advances will be applied within the scientific community to better understand the heterogeneity among extant fish populations in estuarine and oceanic systems and may be used to model exposures and susceptibility to genetic damage and diseases that have environmental etiologies.