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HERO ID
787926
Reference Type
Journal Article
Title
Thyroid disruption by Di-n-butyl phthalate (DBP) and mono-n-butyl phthalate (MBP) in Xenopus laevis
Author(s)
Shen, O; Wu, W; Du, G; Liu, R; Yu, L; Sun, H; Han, X; Jiang, Y; Shi, W; Hu, W; Song, L; Xia, Y; Wang, S; Wang, X
Year
2011
Is Peer Reviewed?
1
Journal
PLoS ONE
EISSN:
1932-6203
Volume
6
Issue
4
Page Numbers
e19159
Language
English
PMID
21544203
DOI
10.1371/journal.pone.0019159
Web of Science Id
WOS:000290015800048
URL
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3081329/pdf/pone.0019159.pdf
Exit
Relationship(s)
is supplemented by
5353598
[Supplementary material]
Abstract
Di-n-butyl phthalate (DBP), a chemical widely used in many consumer products, is estrogenic and capable of producing seriously reproductive and developmental effects in laboratory animals. However, recent in vitro studies have shown that DBP and mono-n-butyl phthalate (MBP), the major metabolite of DBP, possessed thyroid hormone receptor (TR) antagonist activity. It is therefore important to consider DBP and MBP that may interfere with thyroid hormone system.
Nieuwkoop and Faber stage 51 Xenopus laevis were exposed to DBP and MBP (2, 10 or 15 mg/L) separately for 21 days. The two test chemicals decelerated spontaneous metamorphosis in X. laevis at concentrations of 10 and 15 mg/L. Moreover, MBP seemed to possess stronger activity. The effects of DBP and MBP on inducing changes of expression of selected thyroid hormone response genes: thyroid hormone receptor-beta (TRβ), retinoid X receptor gamma (RXRγ), alpha and beta subunits of thyroid-stimulating hormone (TSHα and TSHβ) were detected by qPCR at all concentrations of the compounds. Using mammalian two-hybrid assay in vitro, we found that DBP and MBP enhanced the interactions between co-repressor SMRT (silencing mediator for retinoid and thyroid hormone receptors) and TR in a dose-dependent manner, and MBP displayed more markedly. In addition, MBP at low concentrations (2 and 10 mg/L) caused aberrant methylation of TRβ in head tissue.
The current findings highlight potential disruption of thyroid signalling by DBP and MBP and provide data for human risk assessment.
Keywords
Animals; Dibutyl Phthalate/ pharmacology; Phthalic Acids/ pharmacology; Protein Binding/drug effects; Receptors, Thyroid Hormone/antagonists & inhibitors; Retinoid X Receptor gamma/genetics/metabolism; Thyroid Gland/ drug effects/ metabolism; Thyroid Hormone Receptors beta/genetics/metabolism; Thyrotropin/genetics/metabolism; Xenopus laevis
Edition
2011/05/06
ISBN
1932-6203
Tags
IRIS
•
Dibutyl Phthalate (DBP)
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