Honors College Thesis
 

Mono-substituted isopropylated triaryl phosphate, a major component of Firemaster 550, is anAHR agonist that exhibits AHR-independent cardiotoxicity in zebrafish

Public Deposited

Downloadable Content

Download PDF
https://ir.library.oregonstate.edu/concern/honors_college_theses/fb494b17q

Descriptions

Attribute NameValues
Creator
Abstract
  • Firemaster 550 (FM550) is an additive flame retardant mixture used within polyurethane foam and is increasingly found in house dust and the environment due to leaching. In this study, we sought to investigate mono-substituted isopropylated triaryl phosphate (mITP), a major component of FM550, which has been shown to cause cardiotoxicity during zebrafish embryogenesis. Previous research showed that developmental defects are rescued using an aryl hydrocarbon receptor (AHR) antagonist (CH223191). As zebrafish have three known AHR isoforms, we used a functional AHR2 knockout line along with AHR1A- and AHR1B-specific morpholinos to determine which AHR isoform, if any, mediates mITP-induced cardiotoxicity. As in silico structural homology modeling predicted that mITP may bind favorably to both AHR2 and AHR1B isoforms, we evaluated AHR involvement in vivo by measuring CYP1A expression following exposure to mITP in the presence or absence of CH223191 or AHR-specific morpholinos. Based on these studies, we found that mITP interacts with both AHR2 and AHR1B isoforms to induce CYP1A expression. However, knockdown of all three AHR isoforms failed to block mITP-induced cardiotoxicity in the absence of detectable CYP1A induction. Overall, these results suggest that, while mITP is an AHR agonist, mITP causes AHR-independent cardiotoxicity through a pathway that is also antagonized by CH223191. Keywords: aryl hydrocarbon receptor (AHR), Firemaster 550, flame retardant, CH223191
License
Resource Type
Date Available
Date Issued
Degree Level
Degree Name
Degree Field
Degree Grantor
Commencement Year
Advisor
Non-Academic Affiliation
Rights Statement
Funding Statement (additional comments about funding)
  • NIEHS P30 ES000210, P42 ES016465, Undergraduate Research, Innovation, Scholarship and Creativity (URISC) summer research fellowship, and Honors Experience and Honors Excellence funds
Publisher
Peer Reviewed
Language
Replaces

Relationships

Parents:
In Collection:

Items

Thumbnail Title Date Uploaded Visibility Actions
file details CoryVGerlach_HonorsThesis.pdf 07/26/2017 Public
file details Gerlach_DefensePresentationfinal.pdf 07/26/2017 Public