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THYROID AXIS INHIBITION IN XENOPUS LAEVIS: DEVELOPMENT OF AN AMPHIBIAN-BASED SCREENING ASSAY
Citation:
Degitz, S J., G W. Holcombe, K. M. Flynn, J J. Korte, R C. Kolanczyk, P A. Kosian, AND J E. Tietge. THYROID AXIS INHIBITION IN XENOPUS LAEVIS: DEVELOPMENT OF AN AMPHIBIAN-BASED SCREENING ASSAY. Presented at 2002 SETAC Annual Meeting, Salt Lake City, UT, November 16-20, 2002.
Description:
In response to the initial EDSTAC recommendations, research was conducted on the development of a Xenopus laevis based tail resorption assay for evaluating thyroid axis disruption. These experiments highlighted key limitations associated with relying on tail resorption as a measure of anti/thyroid activity -- the most critical being that tail tissue of tadpoles in metamorphic climax are insensitive to perturbation by agonists/antagonist. To improve on the initial proposal we have conducted experiments comparing the sensitivity of pre-metamorphic (stage 51) and pro-metamorphic (stage 54) tadpoles to the model thyroid axis antagonists methimazole (control 6.25, 12.5, 25, 50, 100 mg/L), 6-propylthiouracil (control, 1.25, 2.5, 5, 10, and 20 mg/L) perchlorate (control, 15.6, 62.5, 250, 1000, 4000 up/ml) and iopanic acid (control, 23.4, 93.8, 375, 1500, 6000 ug/ml). Tadpoles were exposed for a two week period, and developmental stage, thyroid size, and histology were examined at 1 and 2 wks after exposure. Methimazole, 6-propylthiouracil, and perchlorate which are thyroid hormone synthesis inhibitors all caused a concentration dependent inhibition of the thyroid axis. Further, these three compounds caused dose dependent changes in thyroid gland morphology. These changes were characterized as reduced colloid, glandular hypertrophy, and cellular hyperplasia. Treatment failed to affect growth, even in tadpoles which experienced significant metamorphic inhibition. As determined from these endpoints, there were only minor differences in sensitivity observed among the 2 stages examined. Iopanic acid, a type II deiodinase inhibitor, surprisingly stimulated metamorphosis. These results indicate that tadpoles in the early stages of metamorphosis are sensitive to thyroid axis inhibition and that development of a short term, diagnostic amphibian-based thyroid screening assay shows considerable promise. This abstract does not necessarily reflect EPA policy.