Cardiogenic Effects of Trichloroethylene and Trichloroacetic Acid Following Exposure during Heart Specification of Avian Development

Trichloroethylene (TCE) and its metabolite trichloroacetic acid (TCA) are common drinking water contaminants in the United States. Both chemicals have been implicated in causing congenital heart defects (CHD) in human epidemiological and animal model studies. However, the latter studies have primari...

Full description

Saved in:

Bibliographic Details
Published in:	Toxicological sciences 2006-11, Vol.94 (1), p.153-162
Main Authors:	Drake, Victoria J., Koprowski, Stacy L., Hu, Norman, Smith, Susan M., Lough, John
Format:	Article
Language:	eng
Subjects:	Animals Apoptosis - drug effects cell proliferation Cell Proliferation - drug effects Chick Embryo congenital heart defects (CHD) Dose-Response Relationship, Drug Endocardium - cytology Endocardium - drug effects Endocardium - embryology Heart - drug effects Heart - embryology Heart Septal Defects - chemically induced Heart Septal Defects - embryology Heart Valve Diseases - chemically induced Heart Valve Diseases - embryology Heart Ventricles - cytology Heart Ventricles - drug effects Heart Ventricles - embryology In Situ Nick-End Labeling Myocytes, Cardiac - drug effects teratogen Teratogens - toxicity Time Factors trichloroacetic acid (TCA) Trichloroacetic Acid - toxicity trichloroethylene (TCE) Trichloroethylene - toxicity
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Trichloroethylene (TCE) and its metabolite trichloroacetic acid (TCA) are common drinking water contaminants in the United States. Both chemicals have been implicated in causing congenital heart defects (CHD) in human epidemiological and animal model studies. However, the latter studies have primarily focused on assessment of cardiac morphology at late embryonic stages. Here, we tested whether treating avian embryos with TCE or TCA during an exposure window encompassing cardiac specification (Hamburger-Hamilton [HH] 3+) until the onset of chambering (HH 17) informs the etiology of CHD at later stages of development. Embryos were exposed to TCE or TCA via direct injection into the yolk, over a range of doses that included each compound's maximum contaminant level as established by the U.S. Environmental Protection Agency. A modified TUNEL (Terminal deoxynucleotide transferase mediated dUTP-biotin Nick-End Labeling) assay indicated that neither compound induced apoptotic cell death in ventricular myocytes or endocardiocytes at HH 18. However, mid-range dosages of TCE increased myocyte and endocardiocyte proliferation by this time, as determined by monitoring BrdU incorporation; in contrast, an intermediate dose of TCA inhibited proliferation in endocardiocytes. These cellular changes had no apparent functional consequences because all measured hemodynamic parameters were normal for TCE- and TCA-exposed embryos at HH 18, HH 21, and HH 23. In summary, TCE or TCA exposure during the cardiac specification window has only minimal effects on the developing avian heart. These results sharply contrast with our previously reported observations following administration of equivalent doses during a window of valvuloseptal morphogenesis. Taken together, these findings indicate that, as for other teratogens, sensitivity is dictated by the embryo's stage of development.
ISSN:	1096-6080 1096-0929