Cardiovascular Toxicity of Environmental Contaminants to Developing Fish -- Molecular Mechanisms.
Abstract
Both developing zebrafish and medaka are exquisitely sensitive to the cardiovascular toxicity of all-trans retinoic acid (RA) between fertilization and the onset of blood circulation, with incubation medium concentrations of 3-5 ng/ml applied during the blastula stage causing pericardial edema with subsequent circulatory stasis and severe subcutaneous edema and ascites. The sensitivity of both species to RA decreased dramatically during development, with over 40 ng/ml required to cause edema with embryos treated after body pigmentation, and over 300 ng/ml required to cause edema in hatched fry. Zebrafish and medaka embryos are comparably sensitive to the cardiovascular toxicity of TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin when treated at fertilization, with 2-3 ng/g TCDD in embryos causing lethality. Thus these species are approximately 40X less sensitive to the cardiovascular toxicity and lethality caused by TCDD exposure early in development than are lake trout embryos in which the LCSO is 0.065 ng/g. Both fish species demonstrate a TCDD cardiovascular toxicity syndrome similar to that seen following RA exposure, with initial pericardial edema followed by circulatory stasis, subcutaneous edema and ascites. Histologic lesions in TCDD-treated zebrafish included ballooning degeneration and necrosis of brain and epithelial tissues such as kidney, pancreas and liver. Molecular components of basement membrane of cardiovascular and epithelial tissues, including fibronectin, collagen IV and laminin, have been revealed in frozen sections of zebrafish and medaka using immunoperoxidase or immunofluorescence detection methods.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 1995
- Accession Number
- ADA305805
Entities
People
- Jan M. Spitsbergen
Organizations
- Cornell University