PCBs和PBDEs对人类癌细胞和斑马鱼胚胎的毒性对比(英文)Comparative Toxicity of PCBs and PBDEs Using Human Cancer Cell Lines and Zebrafish Embryos
沈华萍;黄长江;陆芳;杨军华;TANGUAY Robert;孙鲁浙;董巧香;
摘要(Abstract):
研究了6种多氯联苯(PCBs)3,3′,4,4′-四氯联苯(PCB77)、2,3,3′,4,4′-五氯联苯(PCB105)、2,3′,4,4′,5-五氯联苯(PCB118)、3,3′,4,4′,5-五氯联苯(PCB126)、2,3,3',4,4',5-六氯联苯(PCB156)和商业型混合多氯联苯Aroclor1254,两种多溴联苯醚(PBDEs)2,2′,4,4′-四溴二苯醚(PBDE47)、十溴二苯醚(PBDE209)对人类癌细胞生长和斑马鱼脱膜与不脱膜胚胎发育的影响.8种化合物均使用0.01、0.1、1.0、10μmol·L-14个浓度进行1~6d的暴露实验.结果表明,PBDE209在最高浓度10μmol·L-1下对结肠癌细胞HCT116(暴露3d后)和RKO(暴露5d后)具有显著的生长抑制作用,所有化合物均对乳腺癌细胞没有显著影响.相比之下,化合物对受精后5~6h(5~6hpf)的斑马鱼胚胎的毒性效应显得比较明显,而各化合物对胚胎的致畸和致死效应又不相同,其毒性强弱依次为PCB126≈PCB156>PCB1254(Aroclor1254)>PBDE47>PCB77>PCB105≈PCB118≈PBDE209.其中PBDE209在未脱膜暴毒后均无致畸与致死现象,脱膜暴毒后最高浓度才表现出显著意义的致畸作用,而PBDE47在最高浓度下可产生高达80%的致畸率,这说明胚胎绒毛膜具有有效阻挡大分子物质如PBDE209进入的作用.PCBs的毒性效应与其空间结构密切相关.如PCB126和PCB105具有相同的分子式,前者在1μmol·L-1下就引起了显著的致死和致畸效应,而后者即使在10μmol·L-1下也没有显著的效应.实验结果也说明不同类型的实验对象所展示的毒性效应并不相同,化合物对体外培养的细胞和发育中的胚胎具有不同的影响.
关键词(KeyWords): 多氯联苯;多溴二苯醚;人类癌细胞;斑马鱼胚胎;毒性
基金项目(Foundation): Supported by the Major Project of Science and Technology Department of Zhejiang Province(No.2008C03001-2);; Key Project of Natural Science Foundation of Zhejiang Province(No.Z2080266);; Key Project of Science and Technology Department of Wenzhou(No.S20060023);; 5010Key Projects of Wenzhou Medical College(No.XNK06009;No.XNK06012);; NIH Grant R01CA079683
作者(Author): 沈华萍;黄长江;陆芳;杨军华;TANGUAY Robert;孙鲁浙;董巧香;
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参考文献(References):
- Beckett K J,Yamini B,Bursian S J.2008.The effects of3,3′,4,4′,5-pentachlorobiphenyl(PCB126)on mink(Mustela vison)reproduction and kit survivability and growth[J].Archives ofEnvironmental Contaminaton and Toxicology,54(1):123-129
- Cantón R F,Sanderson J T,Nijmeijer S,Bergman A,Letcher RJ,Van den Berg M.2006.In vitro effects of brominated flameretardants and metabolites on CYP17catalytic activity:A novelmechanism of action?[J].Toxicology and Applied Pharmacology,216(2):274-281
- Coburn C G,Currás-Collazo M C,Kodavanti P R.2008.Invitro effects of environmentally relevant polybrominated diphenylether(PBDE)congeners on calcium buffering mechanisms in ratbrain[J].Neurochemical Research,33(2):355-364
- Covaci A,Voorspoels S,De Boer J.2003.Determination ofbrominated flame retardants,with emphasis on polybrominateddiphenyl ethers(PBDEs)in environmental and human samples-areview[J].Environment International,29(6):735-756
- Darnerud P O,Eridsen G S,Jóhannesson T,Larsen P B,VilukselaM.2001.Polbrominated diphenyl ethers:occurrence,dietaryexposure,and toxicology[J].Environmental Health Perspectives,109(Suppl1):49-68
- Demersl A,Ayotte P,Brisson J,Dodin S,Robert J,DewaillyE.2002.Plasma concentrations of polychlorinated biphenyls andthe risk of breast cancer:A congener-specific analysis[J].American Journal of Epidemiology,155(7):629-635
- Eriksson P,Fischer C,Wallin M,Jakobsson E,Fredriksson A.2006.Impaired behaviour,learning and memory,in adult miceneonatally exposed to haxabromocyclododecane(HBCDD)[J].Environmental Toxicology and Pharmacology,21(3):317-322
- Grinwis G C M,Van den Brandhof E J,Engelsma M Y,KuiperR V,Vaal M A,Vethaak A D,Weater P W,Vos J G.2001.Toxicity of PCB-126in European flounder(Platichthys flesus)with emphasis on histopathology and cytochrome P4501Ainduction in several organ systems[J].Archives of Toxicology,75(2):80-87
- Hill A J,Teraoka H,Heideman W,Peterson R E.2005.Zebrafishas a model vertebrate for investigating chemical toxicity[J].Toxicological Sciences,86(1):6-9
- Hu X Z,Xu Y,Hu D C,Hui Y,Yang F X.2007.Apoptosisinduction on human hepatoma cells Hep G2of decabrominateddiphenyl ether(PBDE-209)[J].Toxicology Letters,171(1-2):19-28
- Kimbrough R D.1995.Polychlorinated biphenyls(PCBs)andhuman health:an update[J].Critical Review in Toxicology,25(2):133-163
- Kuriyama S N,Talsness C E,Grote K,Chahoud I.2005.Developmental exposure to low-dose PBDE-99:effects on malefertility and neurobehavior in rat offspring[J].EnvironmentalHealth Perspectives,113(2):149-154
- Lavoie E T,Wiley F,Grasman K A.2007.Effect of in ovoexposure to an organochlorine mixture extracted from doublecrested cormorant eggs(Phalacrocorax auritus)and PCB126onimmune function of juvenile chickens[J].Archives of EnvironmentalContamination and Toxicology,53(4):655-661
- Li J Y,Li H,Lei F,Wu D S,Li S F,Li H H.2005.Metaanalysis on relationship between PCBs and human breast cancer[J].Chinese Journal of Public Health,21(7):769-771(inChinese)
- Madia F,Giordano G,Fattori V,Vitalone A,Branchi I,CaponeF,Costa L G.2004.Differential in vitro neurotoxicity of theflame retardant PBDE-99and of the PCB Aroclor1254inhuman astrocytoma cells[J].Toxicology Letters,154(1-2):11-21
- Messeri M D,Bickmeyer U,Weinsberg F,Wiegand H.1997.Congener specific effects by polychlorinated biphenyls oncatecholamine content and release in chromaffin cells[J].Archives of Toxicology,71(7):416-421
- Naert C,Piette M,Bruneel N,Peteghem C V.2006.Occurrenceof polychlorinated biphenyls and polybrominated diphenyl ethersin belgian human adipose tissue samples[J].Archives ofEnvironmental Contamination and Toxicology,50(2):290-296
- Peters A K,Sanderson J T,Bergman A,Van den Berg M.2006.Antagonism of TCDD-induced ethoxyresorufin-O-deethylationactivity by polybrominated diphenyl ethers(PBDEs)in primarycynomolgus monkey(Macaca fascicularis)hepatocytes[J].ToxicologyLetters,164(2):123-132
- Quabius E S,Nolan D T,Segner H,Wendelaar Bonga S E.2002.Confinement stress and starvation modulate the induction ofEROD activity after dietary exposure to PCB126in theMozambique tilapia(Oreochromis mossambicus)[J].Fish Physisologyand Biochemistry,25(2):109-119
- Sakai S,Hayakawa K,Oskamoto K,Takatukai H.2002.Timetrends and horizontal distribution of polybromianted diphenylethers(PBDEs)in sediment cores from Osaka Bay,Japan[J].Organohalogen Compounds,58:189-192
- Siddiqi M A,Laessig R H,Reed K D.2003.PolybrominatedDiphenyl Ethers(PBDEs):New Pollutants-Old Diseases[J].ClinMed Res,4(1):281-290
- Stapleton H M,Baker J E.2003.Comparing polybrominateddiphenyl ether and polychlorinated biphenyl bioaccumulation in afood web in Grand Traverse Bay,Lake Michigan[J].Archivesof Environmental Contamination and Toxicology,45(2):227-234
- Talsness C E,Shakibaei M,Kuriyana S N,Grande S W,KockA S,Schnitker P,DeSouza C,Grote K,Chahoud I.2005.Ultrastructural changes observed in rat ovaries following in uteroand lactational exposure to low doses of a polybrominated flameretardant[J].Toxicology Letters,157(3):189-202
- Van den Heuvel R L,Leppens H,Schoeters G E R.2001.Useof in vitro assays to assess hematotoxic effects of envirmentalcompounds[J].Cell Biology and Toxicology,17(2):107-116
- Wang X Q,Kelow D.2001.Effects of2,2′,4,4′-and3,3′,4,4′-tetrachlorobiphenyls(TCB)on in vitro fertilization in the mouse[J].Chinese Journal of Applied and Environmental Biology,7(6):563-567(in Chinese)
- Watanabe I,Sakai S I.2003.Environmental release and behaviorof brominated flame retardants[J].Environment International,29(6):665-682
- Westerfield M.1995.The Zebrafish Book:A Guide for theLaboratory Use of Zebrafish(danio rerio)(4th edition)[M].Oregon:Univof Oregon Press
- Zhou T,Ross D G,DeVito M J,Crofton K M.2001.Effectsof short-term in vivo exposure to polybrominated diphenyl etherson thyroid hormones and hepatic enzyme activities in weanlingrates[J].Toxicolgical Sciences,61(1):76-82
- Zoeller T.2005.Environmental chemicals as thyroid hormoneanalogues:new studies indicated that thyroid hormone receptorsare targets of industrial chemicals?[J].Molecular and CellularEndocrinology,242(1-2):10-15