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Alterations in gene expression as a mechanism of toxicant.

Hines-R; Ma-Q; Andrews-G; Mirkes-P
Toxicologist 2002 Mar; 66(1-S):1
Over the last several years, it has become apparent that many environmental toxicants exert their effects by the activation or disruption of specific signaling pathways, ultimately resulting in alterations in gene expression. With the completion of the human genome project and the advent of many powerful new technologies, there has been a revolution in our understanding of these mechanisms on the molecular level. The proposed continuing education course is designed to review our current state of knowledge regarding toxicant-induced alterations in gene expression and also identify future directions and research opportunities. The first speaker will focus on our current understanding of the mechanism(s) whereby four receptors, i.e., the Ah receptor (AhR), the Constitutive Androstane Receptor (CAR), the Pregnane X Receptor (PXR), and the Peroxisome Proliferator Activated Receptor (PPAR), mediate the toxicity of four broad classes of chemicals. In contrast to these specific receptor mechanisms, metals exert their toxicity through both stress-response pathways, as well as specific metal-responsive transcription factors. The second speaker will focus on our current understanding of these pathways of toxicant action. The third speaker will review the many exciting discoveries in our understanding of how toxicants alter gene expression during specific windows of development and thereby exert their teratogenic effects. Finally, the fourth speaker will discuss the role of tissue-selective transcription factors on the expression of xenobiotic metabolizing enzymes and how this process impacts toxicant susceptibility. As an advanced course, this curriculum should appeal to toxicologists whose research is in or immediately peripheral to this focus area, but who are interested in gaining a better understanding of the overall subject and its future direction.
Metals; Toxic-materials; Toxicology; Genotoxic-effects; Gene-mutation; Teratogenesis; Reproductive-effects; Reproductive-hazards; Training; Education
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The Toxicologist. Society of Toxicology 41st Annual Meeting and ToxExpo, March 17-21, 2002, Nashville, Tennessee