EPA Science Inventory

Teratogenic impact of dioxin-activated AHR in laboratory animals

Citation:

ABBOTT, B. D. Teratogenic impact of dioxin-activated AHR in laboratory animals. Chapter 17, Raimo Pohjanvitra, D.V.M, Ph.D. (ed.), The AH Receptor in Biology and Toxicology. John Wiley & Sons, Inc, Hoboken, NJ, , 257-266, (2011).

Description:

AHR and ARNT are expressed in mouse and human palatal shelves and in the urinary tract of the mouse fetus. AHR expression, translocation to the nucleus, binding to DRE, and activation are required for mediation of TCDD-induction of CP and HN. Although the human palate requires a higher exposure than the mouse, cellular responses to TCDD exposure are similar in the mouse and human palates, with induction of proliferation of medial epithelial cells and differentiation to a stratified, squamous epithelium that blocks fusion of the opposing shelves. AHR activation by TCDD affects regulation of EGFR and its ligands and TGF{3 family members in palate and urinary tract. EGF appears to playa major role in the induction of CP, but not HN, following AHR activation. The mechanisms for induction of CP and HN appear to differ, however responses appear to involve effects on proliferation and differentiation of epithelial cells. The etiology for AHR-mediated CP and HN is undoubtedly complex and likely to involve interactions between signaling pathways and effects on multiple, tightly regulated cellular processes.

Purpose/Objective:

This book chapter is a contribution to the first book dedicated completely to a presentation of the current understanding of the biology and toxicity associated with activation of the aryl hydrocarbon receptor (AHR). Experts in this field from around the world have been invited to contribute to this book. This chapter discusses over a decade of research by the author in studies of the teratogenicity of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) and the mechanisms through which cleft palate and hydronephrosis are induced by activation of AHR. The chapter places this work in context with the most recent literature 011 the subject and gives this body-of-work a prominent presentation in what is likely to be a high profile book that will serve as a resource to the scientific community for many years.

URLs/Downloads:

Record Details:

Record Type: DOCUMENT (BOOK CHAPTER)
Start Date: 11/10/2010
Completion Date: 11/10/2010
Record Last Revised: 09/21/2016
Record Created: 05/11/2010
Record Released: 05/11/2010
OMB Category: Other
Record ID: 223234

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY

TOXICOLOGY ASSESSMENT DIVISION

DEVELOPMENTAL TOXICOLOGY BRANCH