六溴环十二烷急性暴露对秀丽隐杆线虫的毒性效应
|
摘要
以秀丽隐杆线虫作为模式生物,从生理(体长、运动行为、产卵率),生化(活性氧水平ROS、细胞凋亡水平)及分子(14种胁迫相关基因表达)水平研究六溴环十二烷(HBCD)急性暴露对秀丽隐杆线虫的毒性效应。结果表明,当HBCD急性暴露浓度为20 nmol/L时,只会显著降低秀丽隐杆线虫的运动行为,表明运动行为是最敏感的生理指标。当HBCD急性暴露浓度为200 nmol/L时,秀丽隐杆线虫体内ROS水平和细胞凋亡水平显著提高。当HBCD急性暴露浓度为20～200 nmol/L时,秀丽隐杆线虫体内胁迫相关基因表达量明显上调,主要是氧化应激和细胞凋亡相关基因(hsp-16.2,hsp-16.48,sod-1,sod-3和cep-1)的影响。因此,HBCD可能通过氧化应激和细胞凋亡的途径对线虫产生毒性作用,并且hsp-16.2,hsp-16.48,sod-1,sod-3和cep-1基因具有调控秀丽隐杆线虫的氧化应激和细胞凋亡的作用。
Hexabromocyclododecane(HBCD) is extensively used as an additive brominated flame retardants(BFRs). Due to widespread spectra use of HBCD, it has been found universally in various environmental media including water, sediments, soil, and even in human milk. Moreover, it has multiple toxic effects including developmental toxicity, neurotoxicity and reproductive toxicity. Currently, many toxicological studies of HBCD have been carried out on aquatic organisms and terrestrial species. However, the toxicity of HBCD on soil nematodes is largely unknown. In order to understand toxicological effects along with the changes of stress response by HBCD exposure, the animal model Caenorhabditis elegans was chosen for toxicity study. To fulfill the tasks, nematodes were exposed to various concentrations of HBCD(0, 0.2, 2, 20, 200 nmol/L) up to 24 h. Multiple endpoints along with the physiological levels(growth, reproduction, and locomotion behaviors), reactive oxygen species(ROS) production, degree of cell apoptosis and stress-related gene expressions, were tested on nematodes. Acute exposure to HBCD at different concentrations domain of 0.2～200 nmol/L did not obviously decrease the body bends and body length on nematodes. In contrast, acute exposure to HBCD at the concentration of 20 nmol/L significantly decreased the locomotion behaviors on nematodes, and the locomotion behaviors were most sensitive among the physiological endpoints. Acute exposure to HBCD at the concentration of 200 nmol/L could significantly increase the ROS production followed by the enhancement in degree of cell apoptosis on nematodes. The integrated gene expression profiles visually revealed that exposure to HBCD at the concentration of 200 nmol/L resulted in obvious change of stress-related gene expressions, and the increased expressions were pronounced in several genes related to oxidative stress and cell apoptotic, e.g., hsp-16.2, hsp-16.48, sod-1, sod-3 and cep-1 gene. Therefore, it was speculated that HBCD exposure induced the oxidative stress and cell apoptosis, which resulted in the adverse physiological effects. The hsp-16.2, hsp-16.4, sod-1, sod-3 and cep-1 gene may play important roles in HBCD-induced toxicity, and the oxidative stress and cell apoptosis could be regulated by hsp-16.2, hsp-16.4, sod-1, sod-3 and cep-1 gene. The results are helpful for understanding the toxic effects of HBCD and evaluating the potential risk of HBCD.
Hexabromocyclododecane(HBCD) is extensively used as an additive brominated flame retardants(BFRs). Due to widespread spectra use of HBCD, it has been found universally in various environmental media including water, sediments, soil, and even in human milk. Moreover, it has multiple toxic effects including developmental toxicity, neurotoxicity and reproductive toxicity. Currently, many toxicological studies of HBCD have been carried out on aquatic organisms and terrestrial species. However, the toxicity of HBCD on soil nematodes is largely unknown. In order to understand toxicological effects along with the changes of stress response by HBCD exposure, the animal model Caenorhabditis elegans was chosen for toxicity study. To fulfill the tasks, nematodes were exposed to various concentrations of HBCD(0, 0.2, 2, 20, 200 nmol/L) up to 24 h. Multiple endpoints along with the physiological levels(growth, reproduction, and locomotion behaviors), reactive oxygen species(ROS) production, degree of cell apoptosis and stress-related gene expressions, were tested on nematodes. Acute exposure to HBCD at different concentrations domain of 0.2～200 nmol/L did not obviously decrease the body bends and body length on nematodes. In contrast, acute exposure to HBCD at the concentration of 20 nmol/L significantly decreased the locomotion behaviors on nematodes, and the locomotion behaviors were most sensitive among the physiological endpoints. Acute exposure to HBCD at the concentration of 200 nmol/L could significantly increase the ROS production followed by the enhancement in degree of cell apoptosis on nematodes. The integrated gene expression profiles visually revealed that exposure to HBCD at the concentration of 200 nmol/L resulted in obvious change of stress-related gene expressions, and the increased expressions were pronounced in several genes related to oxidative stress and cell apoptotic, e.g., hsp-16.2, hsp-16.48, sod-1, sod-3 and cep-1 gene. Therefore, it was speculated that HBCD exposure induced the oxidative stress and cell apoptosis, which resulted in the adverse physiological effects. The hsp-16.2, hsp-16.4, sod-1, sod-3 and cep-1 gene may play important roles in HBCD-induced toxicity, and the oxidative stress and cell apoptosis could be regulated by hsp-16.2, hsp-16.4, sod-1, sod-3 and cep-1 gene. The results are helpful for understanding the toxic effects of HBCD and evaluating the potential risk of HBCD.
引文
[1] REMBERGER M, STERNBECK J, PALM A, et al. The environmental occurrence of hexabromocyclododecane in Sweden[J]. Chemosphere, 2004, 54(1): 9-21.
[2] BIRNBAUM L S, STASKAL D F. Brominated flame retardants: Cause for concern?[J]. Environmental Health Perspectives, 2004, 112(1): 9-17.
[3] 李永东, 云霞, 那广水, 等. 环境中六溴环十二烷的研究进展[J]. 环境与健康杂志, 2010, 27(10): 933-936.
[4] YABUSAKI S B, SENGOR S S, FANG Y L. A uranium bioremediation reactive transport benchmark[J]. Computational Geosciences, 2015, 19(3): 551-567.
[5] TAYYEBI A, OUTOKESH M, TAYEBI M, et al. ZnO quantum dots-graphene composites: Formation mechanism and enhanced photocatalytic activity for degradation of methyl orange dye[J]. Journal of Alloys and Compounds, 2016, 663: 738-749.
[6] HEIDARIZAD M, SENGOR S S. Synthesis of Graphene oxide/magnesium oxide nanocomposites with high-rate adsorption of methylene blue[J]. Journal of Molecular Liquids, 2016, 224: 607-617.
[7] HUNZIKER R W, GONSIOR S, MACGREGOR J A, et al. Fate and effect of Hexabromocyclododecane in the environment[J]. Organohalogen Compounds, 2004, 66: 2300-2305.
[8] HE M J, LUO X J, YU L H, et al. Tetrabromobisphenol-A and hexabromocyclododecane in birds from an E-waste region in South China: Influence of diet on diastereoisomer-and enantiomer-specific distribution and trophodynamics[J]. Environmental Science & Technology, 2010, 44(21): 5748-5754.
[9] SPYCHER N F, ISSARANGKUN M, STEWART B D, et al. Biogenic uraninite precipitation and its reoxidation by iron(Iii) (hydr) oxides: A reaction modeling approach[J]. Geochimica Et Cosmochimica Acta, 2011, 75(16): 4426-4440.
[10] HONG H Z, SHEN R, LIU W X, et al. Developmental toxicity of three hexabromocyclododecane diastereoisomers in embryos of the marine medaka Oryzias melastigma[J]. Marine Pollution Bulletin, 2015, 101(1): 110-118.
[11] MARTEINSON S C, BIRD D M, LETCHER R J, et al. Dietary exposure to technical hexabromocyclododecane (HBCD) alters courtship, incubation and parental behaviors in American kestrels (Falco sparverius)[J]. Chemosphere, 2012, 89(9): 1077-1083.
[12] AL-MOUSA F, MICHELANGELI F. The Sarcoplasmic-endoplasmic reticulum Ca2+-atpase (serca) is the likely molecular target for the acute toxicity of the brominated flame retardant hexabromocyclododecane (HBCD)[J]. Chemico-Biological Interactions, 2014, 207: 1-6.
[13] LEUNG M C K, WILLIAMS P L, BENEDETTO A, et al. Caenorhabditis elegans: An emerging model in biomedical and environmental toxicology[J]. Toxicological Sciences, 2008, 106(1): 5-28.
[14] 齐丽娟, 李国君, 马玲, 等. 秀丽隐杆线虫在生态毒理学评价中应用研究进展[J]. 毒理学杂志, 2015, 29(1): 60-65.
[15] VAUX D L, KORSMEYER S J. Cell death in development[J]. Cell, 1999, 96(2): 245-254.
[16] HONG H Z, LI D M, SHEN R, et al. Mechanisms of hexabromocyclododecanes induced developmental toxicity in marine medaka (Oryzias melastigma) embryos[J]. Aquatic Toxicology, 2014, 152: 173-185.
[17] DU M M, ZHANG D D, YAN C Z, et al. Developmental toxicity evaluation of three hexabromocyclododecane diastereoisomers on zebrafish embryos[J]. Aquatic Toxicology, 2012, 112/113: 1-10.
[18] HU X Z, HU D C, XU Y. Effects of tetrabrominated diphenyl ether and hexabromocyclododecanes in single and complex exposure to Hepatoma hepg2 cells[J]. Environmental Toxicology and Pharmacology, 2009, 27(3): 327-337.
[19] KALMAR B, GREENSMITH L. Induction of heat shock proteins for protection against oxidative stress[J]. Advanced Drug Delivery Reviews, 2009, 61(4): 310-318.
[20] ROH J Y, SIM S J, Yi J, et al. Ecotoxicity of silver nanoparticles on the soil nematode caenorhabditis elegans using functional ecotoxicogenomics[J]. Environmental Science & Technology, 2009, 43(10): 3933-3940.
[21] 杨莎莎, 林匡飞, 张卫, 等. 多尺度纳米SiO2对小鼠肝、肾和脾的急性氧化损伤[J]. 华东理工大学学报(自然科学版), 2009, 35(6): 834-838.
[22] SHI D L, LV D M, LIU W X, et al. Accumulation and developmental toxicity of hexabromocyclododecanes (HBCDs) on the marine copepod Tigriopus japonicus[J]. Chemosphere, 2017, 167: 155-162.
[23] ZHANG X, YANG F, ZHANG X, et al. Induction of hepatic enzymes and oxidative stress in chinese rare minnow (Gobiocypris rarus) exposed to waterborne hexabromocyclododecane (HBCDD)[J]. Aquatic Toxicology, 2008, 86: 4-11.
[24] BRENNER S. The genetics of Caenorhabditis elegans[J]. Genetics, 1974, 77: 71.
[25] DENG J, YU L Q, LIU C S, et al. Hexabromocyclododecane-induced developmental toxicity and apoptosis in zebrafish embryos[J]. Aquatic Toxicology, 2009, 93: 29-36.
[2] BIRNBAUM L S, STASKAL D F. Brominated flame retardants: Cause for concern?[J]. Environmental Health Perspectives, 2004, 112(1): 9-17.
[3] 李永东, 云霞, 那广水, 等. 环境中六溴环十二烷的研究进展[J]. 环境与健康杂志, 2010, 27(10): 933-936.
[4] YABUSAKI S B, SENGOR S S, FANG Y L. A uranium bioremediation reactive transport benchmark[J]. Computational Geosciences, 2015, 19(3): 551-567.
[5] TAYYEBI A, OUTOKESH M, TAYEBI M, et al. ZnO quantum dots-graphene composites: Formation mechanism and enhanced photocatalytic activity for degradation of methyl orange dye[J]. Journal of Alloys and Compounds, 2016, 663: 738-749.
[6] HEIDARIZAD M, SENGOR S S. Synthesis of Graphene oxide/magnesium oxide nanocomposites with high-rate adsorption of methylene blue[J]. Journal of Molecular Liquids, 2016, 224: 607-617.
[7] HUNZIKER R W, GONSIOR S, MACGREGOR J A, et al. Fate and effect of Hexabromocyclododecane in the environment[J]. Organohalogen Compounds, 2004, 66: 2300-2305.
[8] HE M J, LUO X J, YU L H, et al. Tetrabromobisphenol-A and hexabromocyclododecane in birds from an E-waste region in South China: Influence of diet on diastereoisomer-and enantiomer-specific distribution and trophodynamics[J]. Environmental Science & Technology, 2010, 44(21): 5748-5754.
[9] SPYCHER N F, ISSARANGKUN M, STEWART B D, et al. Biogenic uraninite precipitation and its reoxidation by iron(Iii) (hydr) oxides: A reaction modeling approach[J]. Geochimica Et Cosmochimica Acta, 2011, 75(16): 4426-4440.
[10] HONG H Z, SHEN R, LIU W X, et al. Developmental toxicity of three hexabromocyclododecane diastereoisomers in embryos of the marine medaka Oryzias melastigma[J]. Marine Pollution Bulletin, 2015, 101(1): 110-118.
[11] MARTEINSON S C, BIRD D M, LETCHER R J, et al. Dietary exposure to technical hexabromocyclododecane (HBCD) alters courtship, incubation and parental behaviors in American kestrels (Falco sparverius)[J]. Chemosphere, 2012, 89(9): 1077-1083.
[12] AL-MOUSA F, MICHELANGELI F. The Sarcoplasmic-endoplasmic reticulum Ca2+-atpase (serca) is the likely molecular target for the acute toxicity of the brominated flame retardant hexabromocyclododecane (HBCD)[J]. Chemico-Biological Interactions, 2014, 207: 1-6.
[13] LEUNG M C K, WILLIAMS P L, BENEDETTO A, et al. Caenorhabditis elegans: An emerging model in biomedical and environmental toxicology[J]. Toxicological Sciences, 2008, 106(1): 5-28.
[14] 齐丽娟, 李国君, 马玲, 等. 秀丽隐杆线虫在生态毒理学评价中应用研究进展[J]. 毒理学杂志, 2015, 29(1): 60-65.
[15] VAUX D L, KORSMEYER S J. Cell death in development[J]. Cell, 1999, 96(2): 245-254.
[16] HONG H Z, LI D M, SHEN R, et al. Mechanisms of hexabromocyclododecanes induced developmental toxicity in marine medaka (Oryzias melastigma) embryos[J]. Aquatic Toxicology, 2014, 152: 173-185.
[17] DU M M, ZHANG D D, YAN C Z, et al. Developmental toxicity evaluation of three hexabromocyclododecane diastereoisomers on zebrafish embryos[J]. Aquatic Toxicology, 2012, 112/113: 1-10.
[18] HU X Z, HU D C, XU Y. Effects of tetrabrominated diphenyl ether and hexabromocyclododecanes in single and complex exposure to Hepatoma hepg2 cells[J]. Environmental Toxicology and Pharmacology, 2009, 27(3): 327-337.
[19] KALMAR B, GREENSMITH L. Induction of heat shock proteins for protection against oxidative stress[J]. Advanced Drug Delivery Reviews, 2009, 61(4): 310-318.
[20] ROH J Y, SIM S J, Yi J, et al. Ecotoxicity of silver nanoparticles on the soil nematode caenorhabditis elegans using functional ecotoxicogenomics[J]. Environmental Science & Technology, 2009, 43(10): 3933-3940.
[21] 杨莎莎, 林匡飞, 张卫, 等. 多尺度纳米SiO2对小鼠肝、肾和脾的急性氧化损伤[J]. 华东理工大学学报(自然科学版), 2009, 35(6): 834-838.
[22] SHI D L, LV D M, LIU W X, et al. Accumulation and developmental toxicity of hexabromocyclododecanes (HBCDs) on the marine copepod Tigriopus japonicus[J]. Chemosphere, 2017, 167: 155-162.
[23] ZHANG X, YANG F, ZHANG X, et al. Induction of hepatic enzymes and oxidative stress in chinese rare minnow (Gobiocypris rarus) exposed to waterborne hexabromocyclododecane (HBCDD)[J]. Aquatic Toxicology, 2008, 86: 4-11.
[24] BRENNER S. The genetics of Caenorhabditis elegans[J]. Genetics, 1974, 77: 71.
[25] DENG J, YU L Q, LIU C S, et al. Hexabromocyclododecane-induced developmental toxicity and apoptosis in zebrafish embryos[J]. Aquatic Toxicology, 2009, 93: 29-36.