Thyroid disruption by Di-n-butyl phthalate (DBP) and mono-n-butyl phthalate (MBP) in Xenopus laevis |
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Authors: | Shen Ouxi Wu Wei Du Guizhen Liu Renping Yu Lugang Sun Hong Han Xiumei Jiang Yi Shi Wei Hu Wei Song Ling Xia Yankai Wang Shoulin Wang Xinru |
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Institution: | The Center for Disease Control and Prevention of Suzhou Industrial Park, Suzhou, China. |
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Abstract: | BackgroundDi-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. Methodology/Principal Findings 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.ConclusionsThe current findings highlight potential disruption of thyroid signalling by
DBP and MBP and provide data for human risk assessment. |
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