Tao Xia

Huazhong University of Science and Technology, Wuhan, Hubei, China

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Publications (36)65.58 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47)-elicited neurotoxicity is associated with neural apoptosis; however the underlying mechanisms remain unclear. To investigate whether the mitochondrial p53 pathway is involved in neuronal apoptosis induced by PBDE-47 and to correlate DNA hypomethylation with p53 activation, human neuroblastoma (SH-SY5Y) cells were treated with different concentrations of PBDE-47 (1, 5, 10μmol/L) for 24h in vitro. The apoptosis and ultrastructural alterations in cells, levels of p53, Bcl-2, Bax, cytochrome c (Cyt c), caspase-3 and methylation status of p53 promoter were determined. Hoechst 33258 staining and transmission electron microscopy analysis showed that PBDE-47 induced SH-SY5Y cells apoptosis characterized by the typical apoptotic morphological changes. In addition, PBDE-47 activated the p53-dependent mitochondrial apoptotic pathway as evidenced by up-regulation of p53 and Bax, down-regulation of Bcl-2 and Bcl-2/Bax ration, enhancement of Cyt c release from mitochondria into the cytosol, activation of caspase-3 as well as ultrastructural abnormalities of mitochondria. However, no obvious decrease in p53 promoter methylation levels was observed in any of the treatment groups by bisulfite genomic sequencing. Collectively, these results suggest that the mitochondrial p53 pathway is involved in PBDE-47-induced SH-SY5Y cells apoptosis, nevertheless p53 promoter hypomethylation may not be implicated in this process.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 10/2013; · 2.99 Impact Factor
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    ABSTRACT: Fluorine, a toxic and reactive element, is widely prevalent throughout the environment and can induce toxicity when absorbed into the body. This study was to explore the possible mechanisms of developmental neurotoxicity in rats treated with different levels of sodium fluoride (NaF). The rats' intelligence, as well as changes in neuronal morphology, glucose absorption, and functional gene expression within the brain were determined using the Morris water maze test, transmission electron microscopy, small-animal magnetic resonance imaging and Positron emission tomography and computed tomography, and Western blotting techniques. We found that NaF treatment-impaired learning and memory in these rats. Furthermore, NaF caused neuronal degeneration, decreased brain glucose utilization, decreased the protein expression of glucose transporter 1 and glial fibrillary acidic protein, and increased levels of brain-derived neurotrophic factor in the rat brains. The developmental neurotoxicity of fluoride may be closely associated with low glucose utilization and neurodegenerative changes.
    Neuromolecular medicine 08/2013; · 5.00 Impact Factor
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    ABSTRACT: Long-term excessive fluoride intake is known to be toxic and can damage a variety of organs and tissues in the human body. However, the molecular mechanisms underlying fluoride-induced male reproductive toxicity are not well understood. In this study, we used a rat model to simulate the situations of human exposure and aimed to evaluate the roles of endoplasmic reticulum (ER) stress and inflammatory response in fluoride-induced testicular injury. Sprague-Dawley rats were administered with sodium fluoride (NaF) at 25, 50 and 100 mg/L via drinking water from pre-pregnancy to gestation, birth and finally to post-puberty. And then the testes of male offspring were studied at 8 weeks of age. Our results demonstrated that fluoride treatment increased MDA accumulation, decreased SOD activity, and enhanced germ cell apoptosis. In addition, fluoride elevated mRNA and protein levels of Glucose-regulated protein 78 (GRP78), inositol requiring ER-to-nucleus signal kinase 1 (IRE1), C/EBP homologous protein (CHOP), indicating activation of ER stress signaling. Furthermore, fluoride also induced testicular inflammation, as manifested by genes up-regulation of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in a nuclear factor-κB (NF-κB)-dependent manner. These were associated with marked histopathological lesions including injury of spermatogonia, decrease of spermatocytes and absence of elongated spermatids, as well as severe ultrastructural abnormalities in testes. Taken together, our results provide compelling evidence that ER stress and inflammation would be novel and significant mechanisms responsible for fluoride-induced disturbance of spermatogenesis and germ cell loss in addition to oxidative stress.
    Toxicology and Applied Pharmacology 05/2013; · 3.98 Impact Factor
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    ABSTRACT: To investigate the effects of sodium fluoride (NaF) on apoptosis, c-Fos mRNA and protein expression levels, and methylation status as well as Dnmt1, Dnmt3a, and Dnmt3b mRNA expression levels in human embryo hepatocyte (L-02) which were exposed to different concentrations of NaF (0, 20, 40, and 80 mg/l) for 24 h in vitro. Results showed that the percentage of apoptosis and c-Fos mRNA and protein expression levels in 40 and 80 mg/l NaF-treated groups were higher than those in the control group (P < 0.05). Further, Dnmt1 mRNA expression level was significantly decreased in the 80 mg/l NaF-treated groups compared to the control group (P < 0.05); Dnmt3a and Dnmt3b mRNA expression levels were significantly decreased in 40 and 80 mg/l NaF-treated groups compared to the control group (P < 0.05). c-Fos methylation levels, according to the bisulfite sequencing results, were decreased in 20, 40, and 80 mg/l NaF-treated groups against the control group. These results suggest that NaF could induce apoptosis and upregulate mRNA and protein expression level of c-Fos as well as decrease mRNA expression levels of Dnmt1, Dnmt3a, and Dnmt3b in L-02 cells. The decrease in c-Fos methylation levels might be involved in the early phase of apoptosis induced by NaF in L-02 cells.
    Biological trace element research 04/2012; 149(1):102-9. · 1.92 Impact Factor
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    ABSTRACT: Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants. As one of the dominant congeners, 2,2', 4,4'-tetrabromodiphenyl ether (PBDE-47) has been shown to be neurotoxic to neuronal cells although the mechanisms remain unclear. To test whether PBDE-47's toxicity was related to endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), human neuroblastoma cells (SH-SY5Y cells) were treated with different concentrations of PBDE-47. Reactive oxygen species (ROS), apoptosis and the expressions of the inositol-requiring enzyme 1 (IRE1) pathway-related molecules were detected. PBDE-47 exposure increased ROS production and activated the UPR by increasing the expressions of glucose-regulated protein 78 (GRP78), IRE1, X-box-binding protein-1 (XBP1), phosphorylation of c-jun N-terminal kinase (JNK) and GADD153/C/EBP homologous protein (CHOP) genes in SH-SY5Y cells. The apoptotic rate increased with the remarkable up-regulation of the Bax/Bcl-2 ratio after IRE1 knockdown, demonstrating the anti-apoptotic role of IRE1. Furthermore, the expressions of CHOP, XBP1 and JNK were down-regulated indicating that IRE1 may activate these key molecules related to apoptosis. PBDE-47 exposure can increase ROS production and activate the IRE1 pathway of the UPR in SH-SY5Y cells contributing to its toxicity. The IRE1 pathway may have both protective and proapoptotic effects on SH-SY5Y cells.
    Toxicology Letters 04/2012; 211(3):325-33. · 3.15 Impact Factor
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    ABSTRACT: The mechanisms underlying the neurotoxicology of endemic fluorosis still remain obscure. To explore lactate dehydrogenase (LDH) leakage, intracellular Ca2+ concentration ([Ca2+]i) and reactive oxygen species (ROS) production induced by fluoride, human neuroblastoma (SH-SY5Y) cells were incubated with sodium fluoride (NaF, 20, 40, 80 mg/L) for 24 h, with 40 mg/L NaF for 3, 6, 12, 18, 24 h, and N-acetyl-L-cysteine (NAC), ethyleneglycol-bis-(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid (EGTA), 1,2-bis(O-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetra(acetoxymethyl) ester (BAPTA-AM) alone or combined with fluoride (40 mg/L) respectively for 12 h in vitro. The results showed that the LDH levels in the 40 and 80 mg/L fluoride-treated groups were significantly higher than that of the control group (in the test level of 0.05, the difference were statistical significance). [Ca2+]i and ROS reached a peak at 3 h and 12 h respectively after exposure to 40 mg/L fluoride. Fluoride coincubated with NAC (antioxidant) dramatically decreased ROS and LDH levels compared with the fluoride only group (in the test level of 0.05, the difference were statistical significance). However, fluoride-induced increase in [Ca2+]i was not affected by NAC. BAPTA-AM (intracellular calcium chelator) markedly lowered fluoride-induced increase of [Ca2+]i, ROS and LDH levels while EGTA (extracellular calcium chelator) have no effects on them. These results indicate that fluoride-related Ca2+ release from the site of intracellular calcium storage causes the elevation of ROS contributing to the cytotoxicity in SH-SY5Y cells. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2011.
    Environmental Toxicology 07/2011; · 2.71 Impact Factor
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    ABSTRACT: Polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) are widespread environmental contaminants. There are potential interactive effects between PBDEs and PCBs, as these compounds share similar structures. The developmental neurotoxicity of 2, 2', 4, 4'-tetrabromodiphenyl ether (PBDE-47) and the interaction of PBDE-47 with 2, 2', 4, 4', 5, 5'-hexachlorobipheny (PCB153) were investigated herein, as the dominant congener forms of PBDEs and PCBs, respectively. SD rats were exposed to a single oral dose of PBDE-47 (1, 5, and 10 μg/g) and/or PCB153 (5 μg/g) on post-natal day (PND) 10. Concentrations of PBDE-47, triiodothyronine (T(3)), thyroxine (T(4)), and thyroid-stimulating hormone (TSH) in serum; organ-to-body weight ratios; as well as long-term learning and memory were measured in 2-month-old rats. The present study found that some doses of PBDE-47 decreased the organ-to-body weight ratios of the thyroid and uterus, decreased the concentration of T(4) in serum, and increased the organ-to-body weight ratio of the ovaries (p < 0.05). PCB153 could increase the action of PBDE-47 during combined exposure, but this interaction was not found between PBDE-47 and PCB153. In a Morris water maze experiment, the latency periods were significantly prolonged and time ratios were obviously depressed in all PBDE-47-treated groups compared to the control (p < 0.05); furthermore, significant interactions between PBDE-47 and PCB153 were observed (p < 0.05). In conclusion, PBDE-47 may depress thyroid development as well as the long-term learning and memory capabilities in adult rats exposed to PBDE-47 on PND 10. PCB153 can interact with PBDE-47, resulting in an increase in developmental neurotoxicity.
    Toxicology and Industrial Health 04/2011; 27(3):279-88. · 1.56 Impact Factor
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    ABSTRACT: The mechanisms underlying fluoride-induced apoptosis in neurons still remain unknown. To investigate apoptosis, caspase-3 activity, and mRNA expression of Fas, Fas-L, and caspases (-3 and -8) induced by fluoride, human neuroblastoma (SH-SY5Y) cells were incubated with 0, 20, 40, and 80 mg/L sodium fluoride (NaF) for 24 h in vitro. The data show that cell viability in the 40 and 80 mg/L fluoride groups were significantly lower than that of the control group. The percentages of apoptosis in the 40 and 80 mg/L fluoride groups were markedly higher than those in the control group, and they increased with the increase in fluoride concentration. The activity of caspase-3 and mRNA expression levels for Fas, Fas-L, and caspases (-3 and -8) in the 40 and 80 mg/L fluoride groups were significantly higher than those in the control group. An agonistic anti-Fas monoclonal antibody (CH-11) significantly augmented apoptosis induction by fluoride, showing a synergistic effect, while a Fas-blocking antibody (ZB4) partly inhibited fluoride-induced apoptosis of SH-SY5Y cells. The results indicate that fluoride exposure could induce apoptosis in SH-SY5Y cells, and the Fas/Fas-L signaling pathway may play an important role in the process.
    Environmental Toxicology 10/2009; 26(1):86-92. · 2.71 Impact Factor
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    ABSTRACT: To explore the effects of PCB153 (2,2,4,4,5,5-hexachlorobiphenyl) on oxidative stress and 8-OHdG (8-hydroxy-2'-deoxyguanosine) content induced by PBDE-47 (2,2,4,4-tetrabromodiphenyl ether) in SH-SY5Y cells. SH-SY5Y cells were incubated with different concentrations of 1, 5, 10 micromol/L PBDE-47 or/and 5 micromol/L PCB153 and antioxidant N-acetyl cysteine (NAC 100 micromol/L) for 24h in vitro, ROS (reactive oxygen species) level and 8-OHdG were measured by using DCFH-DA fluorescent marking method and the skill of high performance liquid chromatogram-electrochemistry (HPLC-EC), respectively. As for ROS formation, there was no significant difference in PBDE-47 groups alone compared to the control group and their corresponding combined groups, respectively (P > 0.05). ROS formation were significantly increased in 5 and 10 micromol/L combined groups compared to the control group and their corresponding concentrations of PBDE-47 groups or PCB153 group, respectively (P < 0.05). 8-OHdG levels were significantly increased in 10 micromol/L PBDE-47, 5 micromol/L PBDE-47 + 5 micromol/L PCB153, and 10 micromol/L PBDE-47 + 5 micromol/L PCB153 groups compared with the control (P < 0.05). 8-OHdG level was dramatically increased in 10 micromol/L PBDE-47 + 5 micromol/L PCB153 groups compared to their corresponding doses of PBDE-47 groups or PCB153 group (P < 0.05). The groups coincubation with N-acetylcysteine caused a decrease in cellular ROS level and ameliorated PBDE-47-mediated oxidative DNA damage effects. Positive relationship was observed between ROS level and 8-OHdG contents (r = 0.895, P < 0.01). These results provide evidence of a direct or indirect relationship between PBDE-47 and oxidative DNA damage. Furthermore, PBDE-47 combined with PCB153 may increase the effects on oxidative DNA damage in SH-SY5Y cells in vitro, oxidative stress may responsible for DNA damage induced by PBDE-47.
    Wei sheng yan jiu = Journal of hygiene research 09/2009; 38(5):513-5.
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    ABSTRACT: To explore the mechanisms underlying the developmental neurotoxic effect of PBDE-47 and its interaction with PCB153, expression levels of mRNA and proteins of the x-chromosome-linked inhibitor of apoptosis protein (XIAP), death associated protein kinase (DAPK), caspase3, caspase12 and cytochrome C in the hippocampus of 2-month-old rats exposed to a single oral dose of PBDE-47 and/or PCB153 on post natal day (PND) 10 were examined. Four levels of PBDE-47 (0, 1, 5, 10 mg/kg) and two levels of PCB153 (0 and 5mg/kg) were added to corn oil in a 4 x 2 factorial completely randomized design study. Meanwhile, the ultrastructures of neurons in the hippocampal CA1 region were observed and the learning and memory capacities were measured in these rats. The results suggested that the mRNA and protein expression levels of all examined genes (with the exception of cytochrome C mRNA in female rats) were significantly changed at some doses (P<0.05); additionally, the total distance swam by rats to reach an escape platform was significantly increased and the ratio of distance taken in the platform quadrant to total distance was notably decreased in all treated groups in the water maze experiment (P<0.05) compared to the control. Numerous alterations were observed in the ultrastructure of neurons in PBDE-47 alone or combination of PBDE-47 and PCB153 groups. Furthermore, an interaction was found between PBDE-47 and PCB153 in lengthening the total distance taken to the platform and decreasing the platform quadrant ratios in the water maze experiment, as well as in the inducing of caspase3, caspase12 and cytochrome C mRNA and protein expression (with exception of cytochrome C mRNA in female rats) in the hippocampus. We conclude that PBDE-47 may induce developmental neurotoxicity in rats via three classic apoptosis pathways, and it may interact with PCB153 to enhance developmental neurotoxicity.
    NeuroToxicology 08/2009; 30(6):1088-95. · 2.65 Impact Factor
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    ABSTRACT: Polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) are important recalcitrant halogenated compounds that have been regarded as major environmental pollutants. Recently, their concurrent appearance in the environment and humans and their structural and toxicological profile similarities have sparked interest in the potential toxicologic consequences of their coexposure. The aim of the current study was to evaluate the cytogenotoxic effects induced by 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47) combined with 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) treatment in human neuroblastoma cells (SH-SY5Y) in vitro. SH-SY5Y cells were exposed to different concentrations of PBDE-47 (0, 2, 4, 8 μM) with or without PCB153 (5 μM) for 24 h. Thereafter, the cell viability, DNA damage, chromosomal abnormalities, and DNA-protein crosslinks (DPC) were determined. The results show that PBDE-47 and PCB153 alone and in combination induce DNA damage, with an increase in the frequency of micronuclei (MN) and DPC formation with increasing PBDE-47 concentration. In cells coexposed to PBDE-47 and PCB153, the cell viability significantly decreased while the MN frequency, DNA damage and DPC formation were all obviously increased compared to those of cells treated with the corresponding concentrations of PBDE-47 or PCB153 alone. Factorial analysis suggests that there were interactions between PBDE-47 and PCB153. The results imply that PBDE-47 interacts with PCB153 to inhibit cell viability and induce DNA damage, DPC formation, and chromosome abnormalities.
    Environmental Toxicology 07/2009; 25(6):564-72. · 2.71 Impact Factor
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    ABSTRACT: Polybrominated diphenyl ethers (PBDEs) are used in large quantities as flame-retardant additives, especially in electrical appliances and textiles. Because of their structural similarity, PBDEs are thought to have toxicities similar to those of polychlorinated biphenyls (PCBs), which are well-known persistent compounds. Both 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47) and 2,2',4,4',5, 5'-hexachlorobiphenyl (PCB153) can coexist in the environment and human tissues as dominant congeners of PBDEs and PCBs, respectively. To explore the mechanisms of the neurotoxic effect of PBDE-47 and the interaction in combination with PCB153, cell viability, lactate dehydrogenase (LDH) leakage, intracellular Ca2+ concentration ([Ca2+]i), apoptosis and expression levels of death associated protein kinase (DAPK), caspase3, caspase12 and cytochrome c mRNA and proteins were measured in SH-SY5Y cells treated with PBDE-47 (0, 1, 5, 10 micromol/L) and/or PCB153 (5 micromol/L) for 24 h. Compared to controls, the cell viabilities were clearly decreased (P<0.05), and LDH leakage, [Ca2+]i and apoptosis were significantly increased (P<0.05). Furthermore, expression levels of DAPK and caspase3 mRNA, caspase12, as well as cytochrome c mRNA and proteins were markedly increased (P<0.05), while pro-caspase3 proteins were significantly decreased (P<0.05). A positive correlation between [Ca2+]i and percentage of apoptotic cells (r=0.86, P<0.05) and an interaction between PBDE-47 and PCB153 (P<0.05) were observed. We conclude that PBDE-47 can induce SH-SY5Y cell apoptosis via three classic apoptosis pathways and interact with PCB153 to enhance neurotoxicity.
    NeuroToxicology 11/2008; 30(1):10-5. · 2.65 Impact Factor
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    ABSTRACT: We studied the relationship between 2,2,4,4-tetrabromodiphenyl ether (PBDE-47) and oxidative DNA damage as well as the mode of interaction between PBDE-47 and 2,2,4,4,5,5-hexachlorobiphenyl (PCB153) by incubating SH-SY5Y cells in four doses of PBDE-47 (0, 1, 5, 10 microM) and/or 5 microM PCB153 and 100 microM NAC (N-acetylcysteine) for 24 h. Results showed that reactive oxygen species (ROS) production in the 5 microM PBDE-47 + PCB153 and 10 microM PBDE-47 + PCB153 groups were significantly higher than that of the control group (p < 0.05). DNA strand breakage and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were significantly increased in the 10 microM PBDE-47, 5 microM PBDE-47 + PCB153, and 10 microM PBDE-47 + PCB153 groups compared with the control (p < 0.05). Furthermore, ROS formation and DNA strand breakage were dramatically increased in the 5 microM PBDE-47 + PCB153 and 10 microM PBDE-47 + PCB153 groups compared with the corresponding PBDE-47 only group and the PCB153 group (p< 0.05). The level of 8-OHdG was significantly increased in the 10 microM PBDE-47 + PCB153 group compared with the corresponding PBDE-47 only group and the PCB153 group (p < 0.05). The PBDE-47 group coincubated with NAC decreased the ROS level and ameliorated PBDE-47-mediated DNA damage. The mRNA expression levels of X-ray repair cross-complementing gene 1 (Xrcc1) were significantly decreased in the 10 microM PBDE-47, 5 microM PBDE-47 + PCB153, and 10 microM PBDE-47 + PCB153 groups, whereas X-ray repair cross-complementing gene 3 (Xrcc3) were significantly increased in the 10 microM PBDE-47 and 10 microM PBDE-47 + PCB153 groups compared with the control (p < 0.05). The PBDE-47 groups coincubated with NAC, however, considerably increased Xrcc1 while decreasing Xrcc3 mRNA expression (p < 0.05). These results indicate that PBDE-47 induced oxidative DNA damage and that PBDE-47 combined with PCB153 may increase such effects in SH-SY5Y cells in vitro. Furthermore, our results suggest that oxidative stress is responsible for DNA damage induced by PBDE-47.
    Toxicological Sciences 10/2008; 107(1):165-70. · 4.33 Impact Factor
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    ABSTRACT: The mechanisms underlying the neurotoxicity of fluorosis still remain obscure. To investigate DNA damage, cell-cycle distribution and expression of nuclear factor kappa B (NF-kappaB) induced by fluoride, the primary rat hippocampal neurons were incubated with various concentrations (20mg/l, 40 mg/l, and 80 mg/l) of sodium fluoride for 24 h in vitro. Our results showed that olive tail moments (OTMs) were significantly elevated in all fluoride-treated groups, while significant increases in the percentage of DNA in the tail were, respectively, observed at 40 mg/l and 80 mg/l levels of fluoride. An increase in the proportion of cells in S-phase was observed in response to the treatment of 40 mg/l and 80 mg/l fluoride. Gene expression of NF-kappaB was also enhanced by fluoride treatment in a dose-dependent manner. The results indicated that fluoride could induce S-phase cell-cycle arrest, up-regulation of NF-kappaB and DNA damage in primary rat hippocampal neurons.
    Toxicology Letters 07/2008; 179(1):1-5. · 3.15 Impact Factor
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    ABSTRACT: To investigate the cyto-genotoxicity of 2, 2', 4, 4'-tetrabromodiphenyl ethers (PBDE-47) combined with 2, 2', 4, 4', 5-hexachlorobiphenyl (PCB153) treatment in SH-SY5Y cells. Exponentially growing SH-SY5Y cells were exposed to different concentrations of PBDE-47 or/and PCB153 for 24 h in vitro. Cell viability, DNA damage, chromosome abnormalities, and DNA-protein crosslinks (DPC) were measured using MTT, comet assay, cytokinesis-block micronucleus (CBMN) test, and SDS-KCl assay respectively. Compared to the each single PBDE-47 groups, the nuclear division index (NDI) was significantly lower (P < 0.05) and the frequencies of micronuclei (MNI), percentage of DNA in the tail, Olive tail moment and DPC were significantly increased (P < 0.05) in the PBDE-47 combined with PCB153 groups. There was a statistical decrease in cell viability in groups of 4 micromol/L PBDE-47 and above combined with PCB153 than that in contrast to the same dose of PBDE-47 group or PCB153 alone (P < 0.05). Significant increase was found in MNI frequency and DPC in 2 micromol/L PBDE-47 and above combined with PCB153 than those in the single PCB153 group (P < 0.05). In the groups of 4 micromol/L PBDE-47 and above combined with PCB153, the cell NDI were significantly lower than that of the single PCB153 group (P < 0.05). Compared to the single PCB153 group, the percentage of DNA in the tail and Olive tail moment was significantly increased in the 8 micromol/L PBDE-47 combined with 5 micromol/L PCB153. Factorial analysis showed that interactions between PBDE-47 and PCB153 existed in inhibiting cell viability, inducing DNA damage, MNI, and DPC formation (P < 0.01), and possessing synergistic effects. Some dose of PBDE-47 combined with PCB153 can inhibit cell viability, induce DNA damage, DPC formation, and chromosome abnormalities. The pattern of the combined effect is synergistic in cyto-genotoxicity.
    Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases 03/2008; 26(2):89-93.
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    ABSTRACT: Polybrominated diphenyl ethers (PBDEs) are an important class of flame retardants. Because of their detection in human breast milk and structural similarity to polychlorinated biphenyls (PCBs), concern has been raised about their potential toxicity, particularly neurotoxic effects in newborns and children. The aim of the current study was to evaluate the cytotoxic and genotoxic effects of 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47) in human neuroblastoma (SH-SY5Y) cells in vitro. SH-SY5Y cells were incubated with different concentrations of PBDE-47 (1, 2, 4, 8 microg/ml) for 24 h, and a set of bioassays were conducted to measure: cell viability, cell proliferation (nuclear division index, NDI), lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS) formation, cell apoptosis, and DNA breakage and cytogenetic damage. The data showed that PBDE-47 inhibited cell viability, increased LDH leakage, and induced cell apoptosis. All significant effects were observed at concentrations of 4 microg/ml and above (P<0.05). After 24 h exposure, a concentration-dependent increase in ROS formation was observed, and there were obviously increase in comparison to the control at concentrations as low as 2 microg/ml PBDE-47. Log-transformed Olive Tail Moment (OTM) were significantly increased compared with the control at various PBDE-47 concentrations (P<0.05), while a significant increase in the percentage of DNA in the tail was only observed at 8 microg/ml PBDE-47 (P<0.05). PBDE-47 caused a concentration-dependent decrease in NDI, and concentration-dependent increases in chromosome abnormalities as measured by total Micronuclei (MNi)/1000 binucleate cells (BNCs), micronucleated binucleate cells (MNBNCs)/1000 BNCs, and nucleoplasmic bridges (NPBs)/1000 BNCs. The results indicate that PBDE-47 is cytotoxic and genotoxic in SH-SY5Y cells in vitro.
    Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 02/2008; 649(1-2):62-70. · 3.90 Impact Factor
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    ABSTRACT: 2,2',4,4'-Tetrabromodiphenyl ether (PBDE-47) causes developmental neurotoxicity in animal studies, but the mechanism remains poorly understood. This paper investigates the mechanism by studying the effects of oxidative stress, DNA damage, and apoptosis induced by PBDE-47 in cultured primary rat hippocampal neurons at different PBDE-47-concentrations (0, 2.06, 20.6, and 41.2 microM). The results showed that reactive oxygen species (ROS) level, percentage of apoptosis, malondialdehyde (MDA) content, the glutathione peroxidase (GSH-Px) level and the lactic dehydrogenase (LDH) leakage rate were affected by exposure of cells to 41.2 microM PDBE-47 (P<0.05), but not to the lower concentrations tested (20.6 and 2.06 microM). Reduced glutathione (GSH), superoxide dismutase (SOD), and increased DNA damage (tested by a comet assay) were affected at all concentrations tested in a dose-related manner (P<0.05). These results suggested that PBDE-47 could induce oxidative stress, DNA damage, and apoptosis in primary rat hippocampal neurons. Whether or not this concentration response pattern indicates that ROS leads to DNA damage and/or apoptosis must be confirmed with further experiments.
    NeuroToxicology 01/2008; 29(1):124-9. · 2.65 Impact Factor
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    ABSTRACT: To investigate the effects of fluoride on the growth and viability, and mRNA and protein expression levels of neural cell adhesion molecules (NCAM) in primary rat hippocampal neurons. The growth and development, the rate of cell survivor, and the mRNA and protein expression levels of NCAM were measured by MTT, RT-PCR, and Western blot respectively after the hippocampal neurons were incubated with 20, 40, and 80 microg/ml sodium fluoride for 24 hours in vitro. As compared with the control group, the number of cells, the length and number of neuritis, and rate of cell survivor were significantly decreased in 80 microg/ml fluoride-treated group (P < 0.05). The mRNA expression levels of NCAM in 40 and 80 microg/ml fluoride-treated groups were significantly lower than that in the control group and decreased with the increasing fluoride concentration. Compared with the control group, the mRNA expression level of NCAM in 20 microg/ml fluoride-treated group was decreased, but the difference was not statistically significant (P > 0.05). The NCAM-180 protein expression levels in 40 and 80 microg/ml fluoride-treated groups, the NCAM-140 protein expression levels in all fluoride-treated groups, and NCAM-120 protein expression level in 80 microg/ml fluoride-treated group were significantly lower than those in the control group (P < 0.05, P < 0.05, P < 0.05, respectively). Fluoride might restrain the growth and survival of rat hippocampal neurons, and decrease mRNA and protein expression levels of NCAM. The impairment of developmental hippocampus might be one of the neurotoxicant target sites for fluoride toxicity.
    Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] 11/2007; 41(6):475-8.
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    ABSTRACT: The mechanisms underlying the neurotoxicity of endemic fluorosis still remain unknown. To investigate the expression level of neural cell adhesion molecules (NCAM), oxidative stress, and apoptosis induced by fluoride, the primary rat hippocampal neurons were incubated with 20, 40, and 80 mg/l sodium fluoride for 24 h in vitro. The results showed that the cell survival rate in the 80 mg/l fluoride-treated group was significantly lower than that of the control group. Forty and 80 mg/l of fluoride induced significantly increased lactate dehydrogenase release, intracellular reactive oxygen species, and the percentage of apoptosis. Compared with control group, the malondialdehyde levels were significantly elevated while glutathione levels and glutathione peroxidase activities were decreased in all fluoride-treated groups, accompanied by the markedly reduced superoxide dismutase activity in 80 mg/l fluoride-treated group. With respect to NCAM mRNA expression levels, a significant dose-dependent decrease was observed in 40 and 80 mg/l fluoride-treated groups against the control group. In addition, as compared to the control group, the protein expression levels of NCAM-180 in 40 and 80 mg/l fluoride-treated groups, NCAM-140 in all fluoride-treated groups, and NCAM-120 in the 80 mg/l fluoride-treated group were significantly decreased. Our study herein suggested that fluoride could cause oxidative stress, apoptosis, and decreased mRNA and protein expression levels of NCAM in rat hippocampal neurons, contributing to the neurotoxicity induced by fluoride.
    Toxicology 08/2007; 236(3):208-16. · 4.02 Impact Factor
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    ABSTRACT: To investigate the oxidative stress and apoptosis induced by 2, 2', 4, 4'-polybrominated diphenyl ethers (PBDE-47) in human neuroblastoma SH-SY5Y cells, and to explore the involved role of reactive oxygen species (ROS) on apoptosis. The rate of cellular survivors, intracellular ROS level, malondialdehyde (MDA) content and percentage of apoptosis were measured respectively after the SH-SY5Y cell were exposed to 2, 4, 8 microg/ml PBDE-47 for 24 h in vitro. The rate of cellular survivors in the low dose PBDE-47-treated group was higher than the control group (P < 0.05), but the moderate and high dose PBDE-47-treated groups were significantly lower than the control group (P < 0.05). The MDA contents in the moderate and high dose PBDE-47-treated groups were significantly higher than the control group (P < 0.05) and increased with increase of PBDE-47 exposure concentrations. Compared with the control group, the levels of ROS were significantly increased with increase of PBDE-47 concentrations (P < 0.05). In the moderate and high dose PBDE-47-treated groups, the percentages of apoptosis were significantly higher than that of the control group (P < 0.05). PBDE-47 can induce oxidative stress and apoptosis in SH-SY5Y cell. ROS may play an important role in the apoptosis induced by PBDE-47.
    Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases 03/2007; 25(3):145-7.

Publication Stats

396 Citations
65.58 Total Impact Points

Institutions

  • 2002–2013
    • Huazhong University of Science and Technology
      • • Key Laboratory of Environment and Health, MOE
      • • School of Public Health
      Wuhan, Hubei, China
  • 2011
    • Guangdong Center for Disease Control and Prevention
      Shengcheng, Guangdong, China
  • 2007
    • Guangdong Pharmaceutical University
      Shengcheng, Guangdong, China
  • 2005–2007
    • Wuhan Centers for Disease Prevention and Control
      Wu-han-shih, Hubei, China