Objective：To investigate the metabolites of polybrominated diphenyl ether 99（BDE-99）and its related cytochrome P450s in an in vitro system.Methods：Rat primary hepatocytes were isolated and treated with BDE-99 for ...Objective：To investigate the metabolites of polybrominated diphenyl ether 99（BDE-99）and its related cytochrome P450s in an in vitro system.Methods：Rat primary hepatocytes were isolated and treated with BDE-99 for 24-72 h.Metabolites were then extracted from the hepatocytes and media,and detected by GC/MS.Several mRNAs of metabolic enzymes were also extracted from the same cells and the gene expression levels were determined using quantitative real-time PCR.In addition,selected recombinant cytochrome P450s（CYPs） were expressed in a bacurovirus/sf9 system,and these were further used to explore the metabolism of BDE-99 in vitro.The parent depletion approach was used for screening the ability of CYPs to eliminate BDE-99.Results： A reductively debrominated metabolite,BDE-47,and three oxidative metabolites,2,4,5-tribromophenol,5-OH-BDE-47,and 5＇-OH-BDE-99,were identified from the BDE-99-treated rat hepatocytes,whereas no MeO metabolite was detected in the system.RT-PCR analysis showed that CYP 3A23/3A1,1A2,and 2B1/2 were induced by BDE-99.Furthermore,using the heterological expressed CYP proteins in in vitro BDE-99 metabolism experiments we found that CYP1A2 and CYP3A4 showed the highest metabolic efficiency for BDE-99,with the metabolic clearance rates of CYP1A2 and CYP3A4 being 30.3%and 27.7%,respectively.CYP1A1 and CYP2A6 displayed relatively low clearance rates,while CYP2E1 seemed not to be associated with the BDE-99 metabolism.Conclusions：In our in vitro rat primary hepatocyte metabolism system,four metabolites of BDE-99 were identified,and CYP3A4 and CYP1A2 were demonstrated to be involved in the BDE-99 metabolism.展开更多
The degradation of 2,2′,4,4′-tetrabromodiphenyl ether(BDE-47) by Pycnoporus sanguineus was investigated in order to explore the impact of the heavy metal Cu2+ on BDE-47 decomposition and the subsequent formation of ...The degradation of 2,2′,4,4′-tetrabromodiphenyl ether(BDE-47) by Pycnoporus sanguineus was investigated in order to explore the impact of the heavy metal Cu2+ on BDE-47 decomposition and the subsequent formation of metabolites, as well as to further elucidate the degradation mechanism of BDE-47. An increase in degradation rate from 18.63% to49.76% in the first four days and its stabilization at(51.26 ± 0.08)% in the following days of BDE-47 incubation were observed. The presence of Cu2+ at 1 and 2 mg/L was found to promote the degradation rate to 56.41% and 60.79%, respectively, whereas higher level of Cu2+(≥ 5 mg/L) inhibited the removal of BDE-47. The similar concentration effects of Cu2+ was also found on contents of fungal protein and amounts of metabolites. Both intracellular and extracellular enzymes played certain roles in BDE-47 transportation with the best degradation rate at 27.90% and 27.67% on the fourth and third day, individually. During the degradation of BDE-47, four types of hydroxylated polybrominated diphenyl ethers(OH-PBDEs), i.e., 6′-OH-BDE-47, 5′-OH-BDE-47, 4′-OH-BDE-17, 2′-OH-BDE-28, and two bromophenols, i.e., 2,4-DBP and 4-BP were detected and considered as degradation products. These metabolites were further removed by P. sanguineus at rates of 22.42%,23.01%, 27.04%, 27.96%, 64.21%, and 40.62%, respectively.展开更多
Polybrominated diphenyl ethers（PBDEs） can be transferred to infants through the ingestion of breast milk, resulting in potential health risk. In this study, PBDEs, hydroxylated polybrominated diphenyl ethers（OH-PB...Polybrominated diphenyl ethers（PBDEs） can be transferred to infants through the ingestion of breast milk, resulting in potential health risk. In this study, PBDEs, hydroxylated polybrominated diphenyl ethers（OH-PBDEs） and 2,2′,4,4′,5,6′-hexachlorobiphenyl（CB-153）in human milk from women living adjacent to e-waste recycling sites of Wenling,China, were investigated. The median level of PBDEs in samples from residents living in the e-waste recycling environment 〉 20 years（R20group, 19.5 ng/g lipid weight（lw））was significantly higher than that for residents living in Wenling 〈 3 years（R3group,3.88 ng/g lw）（p 〈 0.05）, likely ascribable to specific exposure to PBDEs from e-waste recycling activities. In the R20 group, most congeners（except for BDE-209） were correlated with each other（p 〈 0.05）. Moreover, CB-153 showed significant association with most PBDE congeners, rather than BDE-209. The relationship indicated that most BDE congeners other than BDE-209 shared common sources and/or pathways with CB-153, e.g., dietary ingestion. The correlations between BDE-209 and other congeners were different in the two groups, likely suggesting their different exposure sources and/or pathways for PBDEs.Although estimated dietary intake of PBDEs for infants via breast milk was lower than the minimum value affecting human health, the PBDE exposure of infants should be of great concern because of their potential effect on the development of neonates over long-term exposure. OH-PBDEs were not detected in the collected samples, which is in accordance with reports in published literature, likely indicating that they were not apt to be accumulated in human milk.展开更多
The occurrence and fate of hydroxylated polybrominated diphenyl ethers（OH-PBDEs） and methoxylated polybrominated diphenyl ethers（Me O-PBDEs） have received significant attention. However, there is limited informati...The occurrence and fate of hydroxylated polybrominated diphenyl ethers（OH-PBDEs） and methoxylated polybrominated diphenyl ethers（Me O-PBDEs） have received significant attention. However, there is limited information on the metabolism relationship between OH-pentaB DEs and MeO-pentaB DEs that were frequently detected with relatively high concentrations in the environment. In this study, the biotransformation between OH-BDE-99 and MeO-BDE-99 was investigated in rice, wheat, and soybean plants. All the three plants can metabolize OH-BDE-99 to corresponding homologous methoxylated metabolites, while the transformation from MeO-BDE-99 to OH-BDE-99 could only be found in soybean. The conversion of parent compounds was the highest in soybean, followed by wheat and rice. Transformation products were found mainly in the roots, with few metabolites being translocated to the shoots and solution after exposure. The results of this study provide valuable information for a better understanding of the accumulation and transformation of OH-PBDEs and MeO-PBDEs in different plants.展开更多
Naturally produced hydroxylated polybrominated diphenyl ethers(OH-PBDEs)have been extensively studied in the lower end of the Baltic Sea food web.Certain OH-PBDE congeners have displayed increasing concentrations over...Naturally produced hydroxylated polybrominated diphenyl ethers(OH-PBDEs)have been extensively studied in the lower end of the Baltic Sea food web.Certain OH-PBDE congeners have displayed increasing concentrations over the last 30 years in herring(Clupea harengus)from the Baltic proper.However,studies on the top carnivores in the Baltic Sea are scarce.Quantitative data on OH-PBDEs exist for ringed seal(Pusa hispida)from the Gulf of Bothnia,but only a limited amount of data have been produced with regard to Baltic grey seal(Halichoerus grypus),and seals from the Baltic proper.A method was developed and evaluated for quantification of OH-PBDEs in coagulated whole blood.The method was applied on blood obtained from dead grey seals originating from different parts of the Baltic Sea.The levels of OH-PBDEs were observed to be low in the analyzed seals in comparison with reported levels in white-tailed sea eagle nestlings(Halizeetus albicilla),and some Baltic fish species.The levels of the dominant congener,6-OH-BDE47,were statistically significantly higher in seals from the Baltic proper than in seals from the Gulf of Bothnia.Hydroxylated polychlorinated biphenyls(OH-PCBs)were observed to be of much higher concentration than the OH-PBDEs in the analyzed seals.The average concentration of the dominant OH-PCB congener,4-OH-CB107,was one order of magnitude greater than that of 6-OH-BDE47.展开更多
基金supported by 973 program(No.2009CB941701)NSFC grant(No.30972508)MOE Foundation for PhD Program(No 20093234110002)
文摘Objective：To investigate the metabolites of polybrominated diphenyl ether 99（BDE-99）and its related cytochrome P450s in an in vitro system.Methods：Rat primary hepatocytes were isolated and treated with BDE-99 for 24-72 h.Metabolites were then extracted from the hepatocytes and media,and detected by GC/MS.Several mRNAs of metabolic enzymes were also extracted from the same cells and the gene expression levels were determined using quantitative real-time PCR.In addition,selected recombinant cytochrome P450s（CYPs） were expressed in a bacurovirus/sf9 system,and these were further used to explore the metabolism of BDE-99 in vitro.The parent depletion approach was used for screening the ability of CYPs to eliminate BDE-99.Results： A reductively debrominated metabolite,BDE-47,and three oxidative metabolites,2,4,5-tribromophenol,5-OH-BDE-47,and 5＇-OH-BDE-99,were identified from the BDE-99-treated rat hepatocytes,whereas no MeO metabolite was detected in the system.RT-PCR analysis showed that CYP 3A23/3A1,1A2,and 2B1/2 were induced by BDE-99.Furthermore,using the heterological expressed CYP proteins in in vitro BDE-99 metabolism experiments we found that CYP1A2 and CYP3A4 showed the highest metabolic efficiency for BDE-99,with the metabolic clearance rates of CYP1A2 and CYP3A4 being 30.3%and 27.7%,respectively.CYP1A1 and CYP2A6 displayed relatively low clearance rates,while CYP2E1 seemed not to be associated with the BDE-99 metabolism.Conclusions：In our in vitro rat primary hepatocyte metabolism system,four metabolites of BDE-99 were identified,and CYP3A4 and CYP1A2 were demonstrated to be involved in the BDE-99 metabolism.
基金supported by the National Natural Science Foundation of China(Nos.U1501234,41673091,41573091)the National Key Research and Development Program of China(No.2018YFC1802800)
文摘The degradation of 2,2′,4,4′-tetrabromodiphenyl ether(BDE-47) by Pycnoporus sanguineus was investigated in order to explore the impact of the heavy metal Cu2+ on BDE-47 decomposition and the subsequent formation of metabolites, as well as to further elucidate the degradation mechanism of BDE-47. An increase in degradation rate from 18.63% to49.76% in the first four days and its stabilization at(51.26 ± 0.08)% in the following days of BDE-47 incubation were observed. The presence of Cu2+ at 1 and 2 mg/L was found to promote the degradation rate to 56.41% and 60.79%, respectively, whereas higher level of Cu2+(≥ 5 mg/L) inhibited the removal of BDE-47. The similar concentration effects of Cu2+ was also found on contents of fungal protein and amounts of metabolites. Both intracellular and extracellular enzymes played certain roles in BDE-47 transportation with the best degradation rate at 27.90% and 27.67% on the fourth and third day, individually. During the degradation of BDE-47, four types of hydroxylated polybrominated diphenyl ethers(OH-PBDEs), i.e., 6′-OH-BDE-47, 5′-OH-BDE-47, 4′-OH-BDE-17, 2′-OH-BDE-28, and two bromophenols, i.e., 2,4-DBP and 4-BP were detected and considered as degradation products. These metabolites were further removed by P. sanguineus at rates of 22.42%,23.01%, 27.04%, 27.96%, 64.21%, and 40.62%, respectively.
基金supported by the National Natural Science Foundation of China(Nos.21177152,21477157)
文摘Polybrominated diphenyl ethers（PBDEs） can be transferred to infants through the ingestion of breast milk, resulting in potential health risk. In this study, PBDEs, hydroxylated polybrominated diphenyl ethers（OH-PBDEs） and 2,2′,4,4′,5,6′-hexachlorobiphenyl（CB-153）in human milk from women living adjacent to e-waste recycling sites of Wenling,China, were investigated. The median level of PBDEs in samples from residents living in the e-waste recycling environment 〉 20 years（R20group, 19.5 ng/g lipid weight（lw））was significantly higher than that for residents living in Wenling 〈 3 years（R3group,3.88 ng/g lw）（p 〈 0.05）, likely ascribable to specific exposure to PBDEs from e-waste recycling activities. In the R20 group, most congeners（except for BDE-209） were correlated with each other（p 〈 0.05）. Moreover, CB-153 showed significant association with most PBDE congeners, rather than BDE-209. The relationship indicated that most BDE congeners other than BDE-209 shared common sources and/or pathways with CB-153, e.g., dietary ingestion. The correlations between BDE-209 and other congeners were different in the two groups, likely suggesting their different exposure sources and/or pathways for PBDEs.Although estimated dietary intake of PBDEs for infants via breast milk was lower than the minimum value affecting human health, the PBDE exposure of infants should be of great concern because of their potential effect on the development of neonates over long-term exposure. OH-PBDEs were not detected in the collected samples, which is in accordance with reports in published literature, likely indicating that they were not apt to be accumulated in human milk.
基金supported by the National Basic Research Program (973) of China (No. 2014CB441104)National Natural Science Foundation of China (Nos. 21520102009 and 21137003)the Zhejiang Provincial Natural Science Foundation of China (LY14B070009)
文摘The occurrence and fate of hydroxylated polybrominated diphenyl ethers（OH-PBDEs） and methoxylated polybrominated diphenyl ethers（Me O-PBDEs） have received significant attention. However, there is limited information on the metabolism relationship between OH-pentaB DEs and MeO-pentaB DEs that were frequently detected with relatively high concentrations in the environment. In this study, the biotransformation between OH-BDE-99 and MeO-BDE-99 was investigated in rice, wheat, and soybean plants. All the three plants can metabolize OH-BDE-99 to corresponding homologous methoxylated metabolites, while the transformation from MeO-BDE-99 to OH-BDE-99 could only be found in soybean. The conversion of parent compounds was the highest in soybean, followed by wheat and rice. Transformation products were found mainly in the roots, with few metabolites being translocated to the shoots and solution after exposure. The results of this study provide valuable information for a better understanding of the accumulation and transformation of OH-PBDEs and MeO-PBDEs in different plants.
基金This project was financially supported by the Swedish Research Council for the Environment,Agriculture Sciences and Spatial Planning(FORMAS)via the OXPHOS projectby Stockholm University’s Strategic Marine Environment Research Fund,though the Baltic Ecosystem Adaptive Management(BEAM)project.
文摘Naturally produced hydroxylated polybrominated diphenyl ethers(OH-PBDEs)have been extensively studied in the lower end of the Baltic Sea food web.Certain OH-PBDE congeners have displayed increasing concentrations over the last 30 years in herring(Clupea harengus)from the Baltic proper.However,studies on the top carnivores in the Baltic Sea are scarce.Quantitative data on OH-PBDEs exist for ringed seal(Pusa hispida)from the Gulf of Bothnia,but only a limited amount of data have been produced with regard to Baltic grey seal(Halichoerus grypus),and seals from the Baltic proper.A method was developed and evaluated for quantification of OH-PBDEs in coagulated whole blood.The method was applied on blood obtained from dead grey seals originating from different parts of the Baltic Sea.The levels of OH-PBDEs were observed to be low in the analyzed seals in comparison with reported levels in white-tailed sea eagle nestlings(Halizeetus albicilla),and some Baltic fish species.The levels of the dominant congener,6-OH-BDE47,were statistically significantly higher in seals from the Baltic proper than in seals from the Gulf of Bothnia.Hydroxylated polychlorinated biphenyls(OH-PCBs)were observed to be of much higher concentration than the OH-PBDEs in the analyzed seals.The average concentration of the dominant OH-PCB congener,4-OH-CB107,was one order of magnitude greater than that of 6-OH-BDE47.
