PARENT SESSION
WA3 - Toxicology of the Thyroid System
Chair: Brown, Scott1, 1 Environment Canada, Burlington, OH
Co-chair: Digetz, Sig2, 2 US EPA, Duluth, MN
8:00 AM to 12:00 PM - Wednesday, 20 November 2002
Room Ballroom H
(511) cDNA microarray analysis of the effects of the preemergent herbicide, acetochlor, on the Xenopus laevis tail transcriptome during thyroid hormone-induced metamorphosis .
Helbing, Caren*,1, Crump, Doug1, Werry, Kate1, Veldhoen, Nik1, Van Aggelen, Graham2, 1 University of Victoria, Victoria, British Columbia, Canada2 Pacific Environmental Science Centre, Environment Canada, North Vancouver, British Columbia, Canada
ABSTRACT- The thyroid hormones (THs), thyroxine (T4) and 3,5,3′-triiodothyronine (T3), are critical for normal growth, development and homeostasis in vertebrates. This is particularly evident in the absolute requirement of THs for frog tadpole metamorphosis. Tadpole metamorphosis is a rapid, complex postembryonic process in which the tadpole transforms into a juvenile frog. Virtually every tissue is a target for TH action and the dramatic structural and functional changes of larval tissues during metamorphosis have been studied extensively. The major mechanism of TH action involves hormone binding to nuclear TH receptors resulting in tissue-specific activation/repression of gene transcription. A change in tissue-specific gene expression precedes overt morphological change and can be used as a means to identify disruption of TH signaling pathways. Relatively little is known about the effects and identities of endocrine disrupting chemicals (EDCs) that target TH action, particularly at the cellular level. The preemergent herbicide acetochlor [2-chloro-N-(ethoxy-methyl)-N-(2-ethyl-6-methylphenyl) acetamide] is a persistent organic pollutant that can be detected in shallow ground water one year after field application and there is evidence that it can act as an EDC. The presented work addresses the hypothesis that acetochlor may disrupt T3-dependent gene expression programs during metamorphosis of the Pipid frog, Xenopus laevis. In order to do this, we developed a 420-gene cDNA microarray derived from known frog sequences and use this array to determine the effects of acetochlor on precocious metamorphosis. We show that T3-induced metamorphosis is accelerated upon acute exposure to an environmentally relevant level of acetochlor. The morphological changes observed are preceded by alterations in the tadpole tail transcriptome and the nature of these profiles suggest a novel mechanism of action for acetochlor.
Key words: cDNA microarray, frog metamorphosis, thyroid hormone, endocrine disruption