6-HO-BDE-137对大鼠睾丸支持细胞的毒性Toxicity of 6-HO-BDE-137 to Rat Testicular Sertoli Cells
胡伟;李冬梅;韩晓冬;刘红玲;于红霞;
摘要(Abstract)：
以原代培养的大鼠睾丸支持细胞为研究对象,选取环境及生物体中均有检出的一种典型的羟基化PBDE——6-HO-BDE-137作为目标化合物,设置0、0.1、1、10μmol·L-14个浓度梯度,应用噻唑蓝(MTT)试验、荧光显微镜观察和AnnexinV-FITC/PI双染流式细胞术,通过检测大鼠睾丸支持细胞增殖活性、细胞形态和细胞凋亡坏死率的变化,探讨其对支持细胞的损伤情况.研究发现,6-HO-BDE-137显著影响支持细胞的增殖活力,暴露24h,10μmol·L-1浓度组细胞与对照组相比显著增殖(p<0.05),随暴露时间的延长(至48h),10μmol·L-1组转为增殖抑制;支持细胞形态也表现出不同程度的改变,10μmol·L-1浓度组变化最为明显,有大量的细胞变圆飘起;随6-HO-BDE-137暴露浓度的升高,支持细胞死亡率增加,凋亡是支持细胞死亡的主要方式.研究结果提示:6-HO-BDE-137具有生殖毒性.
关键词(KeyWords)： 多溴联苯醚;6-HO-BDE-137;大鼠;睾丸支持细胞
基金项目(Foundation): 国家自然科学基金委员会与香港研究资助局联合基金项目(No.20518002;No.N_CityU110/05);; 国家自然科学基金委员会重点基金项目(No.20737001)
作者(Author): 胡伟;李冬梅;韩晓冬;刘红玲;于红霞;
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DOI:
参考文献(References)：
- Anjaneyulu V,Nageswara Rao K,Radhika P,Muralikrishna M,Connolly J D.1996.A new tetrabromodiphenyl ether from the sponge Dysidea herbacea of the Indian Ocean[J].Indian Journalof Chemistry(Sect.B),35(1):89-90
- Asplund L T,Athanasiadou M,Sjdin A,Bergman,BrjessonH.1999.Organohalogen substances in muscle,egg and bloodfrom healthy baltic Salmon(Salmon Salar)and Baltic Salmon thatproduced offspring with the M74syndrome[J].Ambio,28(1):67-76
- Bowden B F,Towerzey L,Junk P C.2000.A new brominateddiphenyl ether from the marine sponge Dysidea herbacea[J].Australian Journal of Chemistry,53:299-301
- Cameron G M,Stapleton B L,Simonsen S M,Brecknell D J,Garson M J.2000.New sesquiterpene and brominated metabolitesfrom the tropical marine sponge Dysidea sp.[J].Tetrahedron,56(29):5247-5252
- Cantón R F,Sanderson J T,Letcher R J,Bergman,Van denBerg M.2005.Inhibition and induction of aromatase(CYP19)activity by brominated flame retardants in H295R human adrenocorticalcarcinoma cells[J].Toxicological Sciences,88(2):447-455
- Cantón R F,Sanderson J T,Nijmeijer S,Bergman,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
- Capon R,Ghisalberti E L,Jefferies P R,Skelton B W,White AH.1981.Structural studies of halogenated diphenyl ethers from amarine sponge[J].Journal of the Chemical Society PerkinTransactions,1:2464-2467
- CartéB,Faulkner D J.1981.Polybrominated diphenyl ethersfrom Dysidea herbacea,Dysidea chlorea and Phyllospongiafoliascens[J].Tetrahedron,37(13):2335-2339
- Dingemans M M L,Groot A,Kleef R G D M,Bergman,Berg M,Vijverberg H P M,Westerink R H S.2008.Hydroxylation increases the neurotoxic potential of BDE-47toaffect exocytosis and calcium homeostasis in PC12cells[J].Environmental Health Perspectives,116(5):637-643
- Eriksson P,Jakobsson E,Fredriksson A.1998.Developmentalneurotoxicity of brominated flame-retardants,polybrominateddiphenyl ethers and tetrabromo-bis-phenol A[J].OrganohalogenCompounds,35:375-377
- Eriksson P,Jakobsson E,Fredriksson A.2001.Brominated flameretardants:a novel class of developmental neurotoxicants in ourenvironment?[J].Environmental Health Perspectives,109(9):903-908
- Han X D,Gong Y,Tu Z G,Yang P,Chen J X.2005.Theprimary culture and identification of rat Sertoli cells[J].ActaAnatomica Sinica,36(6):682-684(in Chinese)
- Han X D,Wang X Y,Shen S N,Hou Y Y,Chen J X.2004.Effect of nonylphenol on the apoptosis of rat Stertoli cells invitro[J].China Preventive Medicine,5(4):244-248(inChinese)
- Handayani D,Edrada R A,Proksch P,Wray V,Witte L,Van SR W M,Kunzmann A,Soedarson O.1997.Four new bioactivepolybrominated diphenyl ethers of the sponge Dysidea herbacea from West Sumatra,Indonesia[J].Journal of Natural Products,60(12):1313-1316
- He Y H,Murphy M B,Yu R M K,Lam M H W,Hecker M,Giesy J P,Wu R S S,Lam P K S.2008.Effects of20PBDEmetabolites on steroidogenesis in the H295R cell line[J].Toxicology Letters,176(3):230-238
- Kitamura M,Koyama T,Nakano Y,Uemura D.2005.Corallinafuran and corallinaether,novel toxic compounds fromcrustose coralline red algae[J].Chemistry Letters,34(9):1272-1273
- Kitamura S,Shinohara S,Iwase E,Sugihara K,Uramaru N,Shigematsu H,Fujimoto N,Ohta S.2008.Affinity for thyroidhormone and estrogen receptors of hydroxylated polybrominateddiphenyd ethers[J].Journal of Health Science,54(5):607-614
- Krishnamoorthy G,Murugesan P,Muthuvel R,Gunadharini N,Vijayababu M R,Arunkumar A,Venkataraman P,Aruldhas MM,Arunakaran J.2005.Effect of Aroclor1254on Sertolicellular antioxidant system,androgen binding protein and lactatein adult rat in vitro[J].Toxicology,212:195-205
- Kuniyoshi M,Yamada K,Higa T.1985.A biologically activediphenyl ether from the green alga Cladophora fascicularis[J].Cellular and Molecular Life Sciences,41(4):523-524
- Malmvrn A,Marsh G,Kautsky L,Athanasiadou M,Bergma,Asplund L.2005.Hydroxylated and methoxylated brominateddiphenyl ethers in the red algae Ceramium tenuicorne and bluemussels from the Baltic Sea[J].Environmental Science&Technology,39(9):2990-2997
- Malmvrn A,Zebhr Y,Kautsky L,Bergman,Asplund L2008.Hydroxylated and methoxylated polybrominated diphenyethers and polybrominated dibenzo-p-dioxins in red alga andcyanobacteria living in the Baltic Sea Anna Malmv[J]Chemosphere,72(6):910-916
- Marsh G,Athanasiadou M,Athanassiadis I,Sandholm A.2006.Identification of hydroxylated metabolites in2,2′,4,4′-tetrabromodiphenyl ether exposed rats[J].Chemosphere,63(4):690-697
- Meerts I A,Letcher R J,Hoving S,Bergman,Lemmen J G,Burg B V D,Brouwer A.2001.In vitro estrogenicity ofpolybrominated diphenyl ethers,hydroxylated PBDEs,andpolybrominated bisphenol A compounds[J].Environmental HealthPerspectives,109(4):399-407
- Meerts I A T M,Van Zanden J J,Luijks E A C,Leeuwen-BolI,Marsh G,Jakobsson E,Bergman魡,Brouwer A.2000.Potentcompetitive interactions of some brominated flame retardants andrelated compounds with human transthyretin in vitro[J].Toxicological Sciences,56(1):95-104
- Mercado-Feliciano M,Bigsby R M.2008a.Hydroxylatedmetabolites of polybrominated diphenyl ether mixture DE-71areweak estrogen receptor-αligands[J].Environmental HealthPerspectives,116(10):1315-1321
- Mercado-Feliciano M,Bigsby R M.2008b.The polybrominateddiphenyl ether mixture DE-71is mildly estrogenic[J].Environmental Health Perspectives,116(5):605-610
- Mi Y L,Zhang C Q.2005.Toxic and hormonal effects ofpolychlorinated biphenyls on cultured testicular germ cells ofembryonic chickens[J].Toxicology Letters,155(2):297-305
- Moon H B,Kannan K,Lee S J,Choi M.2007.Polybrominateddiphenyl ethers(PBDEs)in sediment and bivalves from Koreancoastal waters[J].Chemosphere,66(2):243-251
- NTP.1986.Toxicology and Carcinogenesis Studies of DecabromodiphenylOxide(CAS No1163-19-5)in R344/N Rats and B6C3F1MiceFeed Sstudies[R].NTP Technical Report Series No309.Research Triangle Park,NC:National Toxicology Program
- Porterfield S P.1994.Vulnerability of the developing brain tothyroid abnormalities:environmental insults to the thyroid system[J].Environmental Health Perspectives,102(Suppl.2):125-130
- Qiu Z Q,Shu W Q,Fu W J,Cao J.2008.Combined effect ofdibutyl phthalate and benzo[a]pyrene in rat sertoli cells in vitro[J].Acta Academiae Medicinae Mlitaristertiae,11(3):1002-1005(in Chinese)
- Raychoudhury S,Kubinski D.2003.Polycyclic aromatic hydrocarbon-induced cytotoxicity in cultured rat Sertoli cells involves differentialapoptotic response[J].Environmental Health Perspectives,111(1):33-38
- Raychoudhury S S,Flowers A F,Millette C F,Finlay M F.2000.Toxic effects of polychlorinated biphenyls on cultured ratSertoli cells[J].Journal of Andrology,21(6):964-973
- Sandala G M,Sonne-Hansen C,Dietz R,Muir D C G,ValtersK,Bennett E R,Born E W,Letcher R J.2004.Hydroxylatedand methyl sulfone PCB metabolites in adipose and whole bloodof polar bear(Ursus maritimus)from East Greenland[J].Scienceof the Total Environment,331(1-3):125-141
- Siddiqi M A,Laessig R H,Reed K D.2003.Polybrominateddiphenyl ethers(PBDEs):new pollutants-old diseases[J].Clinical Medicine&Research,1(4):281-290
- Song R,He Y,Murphy M B,Yeung L W Y,Yu R M K,Lam M H W,Lam P K S,Hecker M,Giesy J P,Wu R S S,Zhang W,Sheng G,Fu J.2008.Effects of fifteen PBDEmetabolites,DE71,DE79and TBBPA on steroidogenesis in theH295R cell line[J].Chemosphere,71(10):1888-1894
- Steinberger A,Klinefelter G.1993.Sensitivity of Sertoli andLeydig cells to xenobiotics in vitro models[J].ReproductiveToxicology,7(Suppl.1):23-27
- Stoker T E,Laws S C,Crofton K M,Hedge J M,Ferrell J M,Cooper R L.2004.Assessment of DE-71,a commercialpolybrominated diphenyl ether(PBDE)mixture,in the EDSP maleand female pubertal protocols[J].Toxicological Sciences,78(1):144-155
- Syed V,Gu W,Hecht N B.1997.Sertoli cells in culture andmRNA differential display provide a sensitive early warning assaysystem to detect changes induced by xenobiotics[J].Journal ofAndrology,11(3):264-273
- Tan J,Cheng S M,Loganath A,Chong Y S,Obbard J P.2007.Polybrominated diphenyl ethers in house dust in Singapore[J].Chemosphere,66(6):985-992
- Thaís F G L,Maria C W A,Catarina S P.2004.Effects ofcarbachol on rat Sertoli cell proliferation and muscarinicacetylcholine receptors regulation:an in vitro study[J].LifeSciences,75(14):1761-1773
- Ueno D,Darling C,Alaee M,Pacepavicius G,Teixeira C,Camobell L,Letcher R J,Bergman魡,Marsh G,Muir D.2008.Hydroxylated polybrominated diphenyl ethers(OH-PBDEs)in theabiotic environment:Surface water and precipitation from Ontario,Canada[J].Environmental Science&Technology,42(5):1657-1664
- Utkina N K,Kazantseva M V,Denisenko V A.1987.Brominateddiphenyl ethers from the marine sponge Dysidea fragilis[J].Chemistry of Natural Compounds,23(4):508-509
- Verreault J,Bech C,Letcher R J,Ropstad E,Dahl E,Gabrielsen G W.2007.Organohalogen contamination in breedingglaucous gulls from the Norwegian Arctic:Associations with basalmetabolism and circulating thyroid hormones[J].EnvironmentalPollution,145(1):138-145
- 韩晓冬,龚昳,屠志刚,杨平,陈建秀.2005.大鼠睾丸支持细胞的原代培养与鉴定[J].解剖学报,36(6):682-684
- 韩晓冬,汪旭莹,沈苏南,侯亚义,陈建秀.2004.壬基酚对体外培养大鼠睾丸支持细胞凋亡影响的研究[J].中国预防医学杂志,5(4):244-248
- 邱志群,舒为群,付文娟,曹佳.2008.邻苯二甲酸二丁酯和苯并[a]芘联合染毒对大鼠睾丸支持细胞的影响[J].第三军医大学学报,11(3):1002-1005