Cytochrome P4501A Induction in Vertebrate Endothelium.
Abstract
This grant examined cytochrome P450 induction in endothelium, a potentially critical yet largely unexplored site of xenobiotic action in vertebrates. The regulation and function of endothelial CYP1A, and its role in toxicity and pharmacokinetics of foreign compounds were examined in porcine and human aorta endothelial cells, and tissues from humans and non-mammalian vertebrates. The first endothelial dose-response to TCDD and first demonstration that endothelial cell CYP1A is catalytically active in intact cells were obtained. Response to different potency AhR agonists was determined. Studies of opportunity examined endothelial CYP1A induction as a marker of exposure, including in human placenta. The possibility that CYP1A in the endothelium might participate in toxicity of Ah receptor agonists was examined in several studies with fish models. The studies: provided new information important for evaluating both the ecological and health risk of chemicals; validated immunohistochemical analysis of CYP1A expression as a biomarker of environmental exposure to diverse compounds of interest to the Air Force; demonstrated endothelial cells as a novel, alternative system for evaluating new chemicals. Ten publications are appended.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 30, 1996
- Accession Number
- ADA325706
Entities
People
- John J. Stegeman
Organizations
- Woods Hole Oceanographic Institution