Tetrabromobisphenol A(TBBPA)is one of the most widely used brominated flame retardants and is extensively used in electronic equipment,furniture,plastics,and textiles.It is frequently detected in water,soil,air,and or...Tetrabromobisphenol A(TBBPA)is one of the most widely used brominated flame retardants and is extensively used in electronic equipment,furniture,plastics,and textiles.It is frequently detected in water,soil,air,and organisms,including humans,and has raised concerns in the scientific community regarding its potential adverse health effects.Human exposure to TBBPA is mainly via diet,respiration,and skin contact.Various in vivo and in vitro studies based on animal and cell models have demonstrated that TBBPA can induce multifaceted effects in cells and animals,and potentially exert hepatic,renal,neural,cardiac,and reproductive toxicities.Nevertheless,other reports have claimed that TBBPA might be a safe chemical.In this review,we re-evaluated most of the published TBBPA toxicological assessments with the goal of reaching a conclusion about its potential toxicity.We concluded that,although low TBBPA exposure levels and rapid metabolism in humans may signify that TBBPA is a safe chemical for the general population,particular attention should be paid to the potential effects of TBBPA on early developmental stages.展开更多
Tetrabromobisphenol A(TBBPA)and its derivatives widely exist in various environments and biota.Although the available data indicate that TBBPA exposure is highly associated with the increased incidence of endometrial ...Tetrabromobisphenol A(TBBPA)and its derivatives widely exist in various environments and biota.Although the available data indicate that TBBPA exposure is highly associated with the increased incidence of endometrial cancer(EC),the effects of TBBPA and its main derivatives on EC proliferation and the involved crucial mechanism remain unclear.The present study aimed to investigate the effects of TBBPA and its derivatives under environmental concentrations on the proliferation of EC,and the crucial mechanism on the progression of EC caused by bromine fame retardants exposure.In this research,TBBPA and two of the most common TBBPA derivatives including TBBPA bis(2-hydroxyethyl ether)(TBBPABHEE)and TBBPA bis(dibromopropyl ether)(TBBPA-BDBPE)were screened for their capacities in induced EC proliferation and explored the related mechanism by in vitro cell culture model and in vivo mice model.Under environmental concentrations,TBBPA promoted the proliferation of EC,the main derivatives of TBBPA(TBBPA-BHEE and TBBPA-BDBPE)did not present the similar facilitation effects.The ubiquitination degradation of p53 was crucial in TBBPA induced EC proliferation,which resulted in the increase of downstream cell cycle and decrease of apoptosis.The further molecular docking result suggested the high affinity between TBBPA and ubiquitinated proteasome.This finding revealed the effects of TBBPA and its derivatives on EC proliferation,thus providing novel insights into the underlying mechanisms of TBBPA-caused EC.展开更多
基金supported by the National Natural Science Foun-dation of China(Nos.21707160 and 21876197)the Chinese Academy of Sciences(No.QYZDJ-SSW-DQC017)the K.C.Wong Education Foundation。
文摘Tetrabromobisphenol A(TBBPA)is one of the most widely used brominated flame retardants and is extensively used in electronic equipment,furniture,plastics,and textiles.It is frequently detected in water,soil,air,and organisms,including humans,and has raised concerns in the scientific community regarding its potential adverse health effects.Human exposure to TBBPA is mainly via diet,respiration,and skin contact.Various in vivo and in vitro studies based on animal and cell models have demonstrated that TBBPA can induce multifaceted effects in cells and animals,and potentially exert hepatic,renal,neural,cardiac,and reproductive toxicities.Nevertheless,other reports have claimed that TBBPA might be a safe chemical.In this review,we re-evaluated most of the published TBBPA toxicological assessments with the goal of reaching a conclusion about its potential toxicity.We concluded that,although low TBBPA exposure levels and rapid metabolism in humans may signify that TBBPA is a safe chemical for the general population,particular attention should be paid to the potential effects of TBBPA on early developmental stages.
基金supported by the Taishan Scholars Program of Shandong Province (No.tsqn201909101)the National Natural Science Foundation of China (Nos.21976114,92043202 and 91943301)。
文摘Tetrabromobisphenol A(TBBPA)and its derivatives widely exist in various environments and biota.Although the available data indicate that TBBPA exposure is highly associated with the increased incidence of endometrial cancer(EC),the effects of TBBPA and its main derivatives on EC proliferation and the involved crucial mechanism remain unclear.The present study aimed to investigate the effects of TBBPA and its derivatives under environmental concentrations on the proliferation of EC,and the crucial mechanism on the progression of EC caused by bromine fame retardants exposure.In this research,TBBPA and two of the most common TBBPA derivatives including TBBPA bis(2-hydroxyethyl ether)(TBBPABHEE)and TBBPA bis(dibromopropyl ether)(TBBPA-BDBPE)were screened for their capacities in induced EC proliferation and explored the related mechanism by in vitro cell culture model and in vivo mice model.Under environmental concentrations,TBBPA promoted the proliferation of EC,the main derivatives of TBBPA(TBBPA-BHEE and TBBPA-BDBPE)did not present the similar facilitation effects.The ubiquitination degradation of p53 was crucial in TBBPA induced EC proliferation,which resulted in the increase of downstream cell cycle and decrease of apoptosis.The further molecular docking result suggested the high affinity between TBBPA and ubiquitinated proteasome.This finding revealed the effects of TBBPA and its derivatives on EC proliferation,thus providing novel insights into the underlying mechanisms of TBBPA-caused EC.
