Dechloranes exhibit binding potency and activity to thyroid hormone receptors

摘要

Dechloranes are a group of halogenated flame retardants with a basic bicyclo[2.2.1]heptene,including Dechlorane Plus(DP),Dechlorane 602(Dec 602),Dechlorane 603(Dec 603)and Dechlorane 604(Dec 604).A few epidemiological investigations and animal experiments have shown that DP exhibited thyroid-interfering effects.In the present study,we investigated whether DP and three other dechloranes could interfere the thyroid function through thyroid hormone receptors(TRs,TRαand TRβ)signaling pathways.The binding affinities of the four dechloranes to the two TRs were determined by fluorescence competitive binding assay.It was found that all the four dechloranes could bind with the two TRs.The relative potency(RP)values ranged from nd(not detectable)to 0.0667.Between the two TRs,dechloranes were more inclined to bind with TRβ,which implies that the thyroid interference effect of dechloranes may have selectivity in different tissues and organs.TRs-mediated luciferase reporter gene assay and T-screen assay showed that all the four dechloranes exhibited antagonistic activity to TRs in the cells.Taken together,our results demonstrated that dechloranes might interfere with thyroid function by binding with TRs and acting as TR antagonists.The health risk of highly exposed human populations should be of serious concern because of the high hazard quotient calculated from our cell assay results.