Investigations into the Molecular Mechanisms of Trichloroethylene Cardiotoxicity in vivo and in vitro

Persistent Link:
http://hdl.handle.net/10150/195364
Title:
Investigations into the Molecular Mechanisms of Trichloroethylene Cardiotoxicity in vivo and in vitro
Author:
Caldwell, Patricia Theresa
Issue Date:
2009
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Trichloroethylene (TCE) is among the most common water contaminant in the United States and around the world. It is estimated that between 9% and 34% of all drinking water sources contain some TCE. The EPA set a drinking water standard for TCE at 5 parts per billion (ppb) in 1989, however since this date, many studies have shown TCE is dangerous to the health of adults and unborn children, even at low-level exposures. These studies reveal exposure to TCE can cause multi-organ damage, especially for the kidney, liver, reproductive and development systems. We investigated how TCE can effect embryonic heart development by identifing possible target mechanisms changing after exposure. Acute and chronic exposure to rat cardiomyocytes produced altered calcium flow and significant changes with TCE doses as low as 10ppb. Embryonic carcinoma cells, rat cardiomyocytes and fetal heart tissue all showed global changes in gene expression after low-dose TCE exposure, including critical ion channels that drive calcium flux. High levels of folic acid supplementation in combination with 10ppb TCE exposure in maternal diets caused significant genetic modifications in mRNA expression levels of Day 10 embryonic mouse cardiac tissue. We also found both high and low folate maternal diets leads to similar phenotypic outcomes in embryo development.
Type:
text; Electronic Dissertation
Keywords:
embryonic heart; environmental toxicant; folate; Ryr2; Serca2a; trichloroethylene
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Pathobiology; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Selmin, Ornella
Committee Chair:
Selmin, Ornella

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titleInvestigations into the Molecular Mechanisms of Trichloroethylene Cardiotoxicity in vivo and in vitroen_US
dc.creatorCaldwell, Patricia Theresaen_US
dc.contributor.authorCaldwell, Patricia Theresaen_US
dc.date.issued2009en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractTrichloroethylene (TCE) is among the most common water contaminant in the United States and around the world. It is estimated that between 9% and 34% of all drinking water sources contain some TCE. The EPA set a drinking water standard for TCE at 5 parts per billion (ppb) in 1989, however since this date, many studies have shown TCE is dangerous to the health of adults and unborn children, even at low-level exposures. These studies reveal exposure to TCE can cause multi-organ damage, especially for the kidney, liver, reproductive and development systems. We investigated how TCE can effect embryonic heart development by identifing possible target mechanisms changing after exposure. Acute and chronic exposure to rat cardiomyocytes produced altered calcium flow and significant changes with TCE doses as low as 10ppb. Embryonic carcinoma cells, rat cardiomyocytes and fetal heart tissue all showed global changes in gene expression after low-dose TCE exposure, including critical ion channels that drive calcium flux. High levels of folic acid supplementation in combination with 10ppb TCE exposure in maternal diets caused significant genetic modifications in mRNA expression levels of Day 10 embryonic mouse cardiac tissue. We also found both high and low folate maternal diets leads to similar phenotypic outcomes in embryo development.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectembryonic hearten_US
dc.subjectenvironmental toxicanten_US
dc.subjectfolateen_US
dc.subjectRyr2en_US
dc.subjectSerca2aen_US
dc.subjecttrichloroethyleneen_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePathobiologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorSelmin, Ornellaen_US
dc.contributor.chairSelmin, Ornellaen_US
dc.contributor.committeememberRunyan, Raymonden_US
dc.contributor.committeememberGuerriero, Vinceen_US
dc.contributor.committeememberJost, B. Helenen_US
dc.contributor.committeememberCollins, Jamesen_US
dc.identifier.proquest10361en_US
dc.identifier.oclc659751974en_US
All Items in UA Campus Repository are protected by copyright, with all rights reserved, unless otherwise indicated.