多氯联苯羟基化代谢物及其雌激素效应研究进展Advances on Hydroxylated Polychlorinated Biphenyls Metabolites and the Estrogenic Effects
黄苑;苏晓鸥;王瑞国;张维;
摘要(Abstract):
多氯联苯作为一种环境内分泌干扰物,具有一定的雌激素干扰效应,导致动物雌激素水平紊乱或功能异常,从而影响生殖、发育或行为。羟基多氯联苯是多氯联苯最主要的活性代谢产物,已经在动物和人体组织中被检出。羟基多氯联苯的化学性质和分子空间构象使其雌激素干扰效应可能较母体化合物更强。因此,它们对人类和动物机体的潜在影响以及由此带来的新的毒理学问题成为内分泌干扰研究领域的热点之一,相关的毒性作用机制需要进一步探索。本文对多氯联苯的代谢途径、羟基多氯联苯在生物体内的暴露水平、雌激素干扰效应及作用机制进行综述。
关键词(KeyWords): 羟基多氯联苯;代谢;雌激素效应
基金项目(Foundation): “国家重点研发计划”(2017YFC1600300)
作者(Author): 黄苑;苏晓鸥;王瑞国;张维;
Email:
DOI:
参考文献(References):
- [1]Kaw H Y,Kannan N.A review on polychlorinated biphenyls(PCBs)and polybrominated diphenyl ethers(PBDEs)in South Asia with a focus on Malaysia[J].Reviews of Environmental Contamination and Toxicology,2016(242):153-181
- [2]杨方星,徐盈.多氯联苯的羟基化代谢产物及其内分泌干扰机制[J].化学进展,2005,17(4):740-748Yang F X,Xu Y.Hydroxylated metabolites of polychlorinated biphenyls and their endocrine disrupting mechanism[J].Progress in Chemistry,2005,17(4):740-748(in Chinese)
- [3]van den Berg M,Kypke K,Kotz A,et al.WHO/UNEPglobal surveys of PCDDs,PCDFs,PCBs and DDTs in human milk and benefit-risk evaluation of breastfeeding[J].Archives of Toxicology,2017,91(1):83-96
- [4]Ma S,Ren G,Zeng X,et al.Polychlorinated biphenyls and their hydroxylated metabolites in the serum of ewaste dismantling workers from eastern China[J].Environmental Geochemistry and Health,2017(6):1-10
- [5]Fernandez-Gonzalez R,Yebra-Pimentel I,Martinez-Carballo E,et al.A critical review about human exposure to polychlorinated dibenzo-p-dioxins(PCDDs),polychlorinated dibenzofurans(PCDFs)and polychlorinated biphenyls(PCBs)through foods[J].Critical Reviews in Food Science and Nutrition,2015,55(11):1590-1617
- [6]Bytingsvik J,Lie E,Aars J,et al.PCBs and OH-PCBs in polar bear mother-cub pairs:A comparative study based on plasma levels in 1998 and 2008[J].Science of the Total Environment,2012,417:117-128
- [7]于洋,马俊花,莫罹,等.北京市密云县潮河周边土壤中类二恶英PCBs分析评价[J].生态毒理学报,2015,10(2):403-410Yu Y,Ma J H,Mo L,et al.Analysis and evaluation of dioxin-like polychlorinated biphenyl in soil along Chao River in Miyun County of Beijing[J].Asian Journal of Ecotoxicology,2015,10(2):403-410(in Chinese)
- [8]Lecomte S,Habauzit D,Charlier T D,et al.Emerging estrogenic pollutants in the aquatic environment and breast cancer[J].Genes,2017,8(9):229
- [9]Dombret C,Capela D,Poissenot K,et al.Neural mechanisms underlying the disruption of male courtship behavior by adult exposure to di(2-ethylhexyl)phthalate in mice[J].Environmental Health Perspectives,2017,125(9):097001
- [10]Bergman A,Klasson-Wehler E,Kuroki H.Selective retention of hydroxylated PCB metabolites in blood[J].Environmental Health Perspectives,1994,102(5):464
- [11]Matthews H B,Anderson M W.Effect of chlorination on the distribution and excretion of polychlorinated biphenyls[J].Drug Metabolism and Disposition,1975,3(5):371-380
- [12]Grimm F A,Hu D,Kania-Korwel I,et al.Metabolism and metabolites of polychlorinated biphenyls[J].Critical Reviews in Toxicology,2015,45(3):245-272
- [13]Routti H,Letcher R J,Arukwe A.Biotransformation of PCBs in relation to phase I and II xenobiotic-metabolizing enzyme activities in ringed seals(Phoca hispida)from Svalbard and the Baltic Sea[J].Environmental Science&Technology,2008,42(23):8952-8958
- [14]Dhakal K,He X,Lehmler H J,et al.Identification of sulfated metabolites of 4-chlorobiphenyl(PCB3)in the serum and urine of male rats[J].Chemical Research in Toxicology,2012,25(12):2796-2804
- [15]Grimm F A,He X,Teesch L M,et al.Tissue distribution,metabolism,and excretion of 3,3'-dichloro-4'-sulfooxy-biphenyl in the rat[J].Environmental Science&Technology,2015,49(13):8087-8095
- [16]Soechitram S D,Athanasiadou M,Hovander L,et al.Fetal exposure to PCBs and their hydroxylated metabolites in a Dutch cohort[J].Environmental Health Perspectives,2004,112(11):1208-1212
- [17]Hovander L,Malmberg T,Athanasiadou M,et al.Identification of hydroxylated PCB metabolites and other phenolic halogenated pollutants in human blood plasma[J].Archives of Environmental Contamination and Toxicology,2002,42(1):105-117
- [18]Mizukawa H,Nomiyama K,Kunisue T,et al.Organohalogens and their hydroxylated metabolites in the blood of pigs from an open waste dumping site in south India:Association with hepatic cytochrome P450[J].Environmental Research,2015,138:255-263
- [19]Berg V,Lyche J L,Gutleb A C,et al.Distribution of PCB 118 and PCB 153 and hydroxylated PCB metabolites(OH-CBs)in maternal,fetal and lamb tissues of sheep exposed during gestation and lactation[J].Chemosphere,2010,80(10):1144-1150
- [20]Houde M,Pacepavicius G.Polychlorinated biphenyls and hydroxylated polychlorinated biphenyls in plasma of bottlenose dolphins(Tursiops truncatus)from the Western Atlantic and the Gulf of Mexico[J].Environmental Science&Technology,2006,40(19):5860-5866
- [21]Weijs L,Das K,Siebert U,et al.Concentrations of chlorinated and brominated contaminants and their metabolites in serum of harbour seals and harbour porpoises[J].Environment International,2009,35(6):842-850
- [22]Campbell L M,Muir D C G,Whittle D M,et al.Hydroxylated PCBs and other chlorinated phenolic compounds in lake trout(Salvelinus namaycush)blood plasma from the Great Lakes Region[J].Environmental Science&Technology,2003,37(9):1720-1725
- [23]Helgason L B,Arukwe A,Gabrielsen G W,et al.Biotransformation of PCBs in Arctic seabirds:Characterization of phase I and II pathways at transcriptional,translational and activity levels[J].Comparative Biochemistry and Physiology Part C:Toxicology&Pharmacology,2010,152(1):34-41
- [24]Jansson B,Jensen S,Olsson M,et al.Identification by GC-MS of phenolic metabolites of PCB and p,p'-DDE isolated from Baltic guillemot and seal[J].Ambio,1975,6:93-97
- [25]Tehrani R,Van Aken B.Hydroxylated polychlorinated biphenyls in the environment:Sources,fate,and toxicities[J].Environmental Science and Pollution Research,2014,21(10):6334-6345
- [26]Gebbink W A,Sonne C,Dietz R,et al.Tissue-specific congener composition of organohalogen and metabolite contaminants in East Greenland polar bears(Ursus maritimus)[J].Environmental Pollution,2008,152(3):621-629
- [27]Gustavson L,Ciesielski T M,Bytingsvik J,et al.Hydroxylated polychlorinated biphenyls decrease circulating steroids in female polar bears(Ursus maritimus)[J].Environmental Research,2015,138:191-201
- [28]Mizukawa H,Nomiyama K,Nakatsu S,et al.Speciesspecific differences in the accumulation features of organohalogen contaminants and their metabolites in the blood of Japanese terrestrial mammals[J].Environmental Pollution,2013,174:28-37
- [29]Imaeda D,Nomiyama K,Kunisue T,et al.Blood levels of polychlorinatedbiphenyls and their hydroxylated metabolites in Baikal seals(Pusa sibirica):Emphasis on interspecies comparison,gender difference and association with blood thyroid hormone levels[J].Chemosphere,2014,114:1-8
- [30]Ochiai M,Nomiyama K,Isobe T,et al.Accumulation of hydroxylated polychlorinated biphenyls(OH-PCBs)and implications for PCBs metabolic capacities in three porpoise species[J].Chemosphere,2013,92(7):803-810
- [31]Rylander C,Lund E,Froyland L,et al.Predictors of PCP,OH-PCBs,PCBs and chlorinated pesticides in a general female Norwegian population[J].Environment International,2012,43:13-20
- [32]Eguchi A,Nomiyama K,Devanathan G,et al.Different profiles of anthropogenic and naturally produced organohalogen compounds in serum from residents living near a coastal area and e-waste recycling workers in India[J].Environment International,2012,47:8-16
- [33]Nomiyama K,Yonehara T,Yonemura S,et al.Determination and characterization of hydroxylated polychlorinated biphenyls(OH-PCBs)in serum and adipose tissue of Japanese women diagnosed with breast cancer[J].Environmental Science&Technology,2010,44(8):2890-2896
- [34]Tobiishi K,Suzuki S,Todaka T,et al.Concentration of hydroxylated polychlorinated biphenyls(OH-PCBs)in the blood of Yusho patients in 2010[J].Fukuoka Igaku Zasshi=Hukuoka Acta Medica,2013,104(4):136-142
- [35]Sandau C D,Ayotte P,Dewailly E,et al.Analysis of hydroxylated metabolites of PCBs(OH-PCBs)and other chlorinated phenolic compounds in whole blood from Canadian Inuit[J].Environmental Health Perspectives,2000,108:611-616
- [36]Fngstr9m B,Athanasiadou M,Grandjean P,et al.Hydroxylated PCB metabolites and PCBs in serum from pregnant Faroese women[J].Environmental Health Perspectives,2002,110:895-899
- [37]Park H Y,Park J S,Sovcikova E,et al.Exposure to hydroxylated polychlorinated biphenyls(OH-PCBs)in the prenatal period and subsequent neurodevelopment in eastern Slovakia[J].Environmental Health Perspectives,2009,117(10):1600
- [38]Eguchi A,Nomiyama K,Minh Tue N,et al.Residue profiles of organohalogen compounds in human serum from e-waste recycling sites in North Vietnam:Association with thyroid hormone levels[J].Environmental Research,2015,137:440-449
- [39]Al-Anati L,Viluksela M,Strid A,et al.Hydroxyl metabolite of PCB 180 induces DNA damage signaling and enhances the DNA damaging effect of benzo[a]pyrene[J].Chemico-Biological Interactions,2015,239:164-173
- [40]Nomiyama K,Hirakawa S,Eguchi A,et al.Toxicological assessment of polychlorinated biphenyls and their metabolites in the liver of Baikal seal(Pusa sibirica)[J].Environmental Science&Technology,2014,48(22):13530-13539
- [41]Dirinck E,Dirtu A C,Malarvannan G,et al.A preliminary link between hydroxylated metabolites of polychlorinated biphenyls and free thyroxin in humans[J].International Journal of Environmental Research and Public Health,2016,13(4):421
- [42]Soechitram S D,Berghuis S A,Visser T J,et al.Polychlorinated biphenyl exposure and deiodinase activity in young infants[J].Science of The Total Environment,2017,574:1117-1124
- [43]Letcher R J,Lu Z,de Solla S R,et al.Snapping turtles(Chelydra serpentina)from Canadian areas of concern across the southern Laurentian Great Lakes:Chlorinated and brominated hydrocarbon contaminants and metabolites in relation to circulating concentrations of thyroxine and vitamin A[J].Environmental Research,2015,143:266-278
- [44]Dreiem A,Rykken S,Lehmler H J,et al.Hydroxylated polychlorinated biphenyls increase reactive oxygen species formation and induce cell death in cultured cerebellar granule cells[J].Toxicology and Applied Pharmacology,2009,240(2):306-313
- [45]史熊杰,刘春生,余珂,等.环境内分泌干扰物毒理学研究[J].化学进展,2009,21(2):340-349Shi X J,Liu C S,Yu K,et al.Toxicological research on environmental endocrine disruptors[J].Progress in Chemistry,2009,21(2):340-349(in Chinese)
- [46]Gregoraszczuk E L,Ptak A,Karniewska M,et al.Action of defined mixtures of PCBs,p,p'-DDT and its metabolite p,p'-DDE,on co-culture of porcine theca and granulosa cells:Steroid secretion,cell proliferation and apoptosis[J].Reproductive Toxicology,2008,26(2):170-174
- [47]Lyche J L,Oskam I C,Skaare J U,et al.Effects of gestational and lactational exposure to low doses of PCBs126 and 153 on anterior pituitary and gonadal hormones and on puberty in female goats[J].Reproductive Toxicology,2004,19(1):87-95
- [48]Connor K,Ramamoorthy K,Moore M,et al.Hydroxylated polychlorinated biphenyls(PCBs)as estrogens and antiestrogens:Structure-activity relationships[J].Toxicology and Applied Pharmacology,1997,145(1):111-123
- [49]Moore M,Mustain M,Daniel K,et al.Antiestrogenic activity of hydroxylated polychlorinated biphenyl congeners identified in human serum[J].Toxicology and Applied Pharmacology,1997,142(1):160-168
- [50]Machala M,Bláha L,Lehmler H-J.Toxicity of hydroxylated and quinoid PCB metabolites:Inhibition of gap junctional intercellular communication and activation of aryl hydrocarbon and estrogen receptors in hepatic and mammary cells[J].Chemical Research in Toxicology,2004,17(3):340-347
- [51]Ptak A,Ludewig G,Lehmler H J,et al.Comparison of the actions of 4-chlorobiphenyl and its hydroxylated metabolites on estradiol secretion by ovarian follicles in primary cells in culture[J].Reproductive Toxicology,2005,20(1):57-64
- [52]Ruiz P,Ingale K,Wheeler J S,et al.3D QSAR studies of hydroxylated polychlorinated biphenyls as potential xenoestrogens[J].Chemosphere,2016,144:2238-2246
- [53]Magoffin D A.Ovarian theca cell[J].The International Journal of Biochemistry&Cell Biology,2005,37(7):1344-1349
- [54]Braathen M,Mortensen A S,Sandvik M,et al.Estrogenic effects of selected hydroxy polychlorinated biphenyl congeners in primary culture of Atlantic salmon(Salmo salar)hepatocytes[J].Archives of Environmental Contamination and Toxicology,2009,56(1):111-122
- [55]李娟,栾新红.类固醇合成急性调节蛋白的生物学特性及作用研究概况[J].动物医学进展,2016,37(1):110-113Li J,Luan X H.Induction to biological characteristics and action mechanisms of steroidogenic acute regulatory protein[J].Progress in Veterinary Medicine,2016,37(1):110-113(in Chinese)
- [56]Canton R F,Sanderson J T,Nijmeijer S,et al.In vitro effects of brominated flame retardants and metabolites on CYP17 catalytic activity:A novel mechanism of action?[J].Toxicology and Applied Pharmacology,2006,216(2):274-281
- [57]Xu Y,Yu R M,Zhang X,et al.Effects of PCBs and MeSO2-PCBs on adrenocortical steroidogenesis in H295R human adrenocortical carcinoma cells[J].Chemosphere,2006,63(5):772-784
- [58]Ptak A,Ludewig G,Robertson L,et al.In vitro exposure of porcine prepubertal follicles to 4-chlorobiphenyl(PCB3)and its hydroxylated metabolites:Effects on sex hormone levels and aromatase activity[J].Toxicology Letters,2006,164(2):113-122
- [59]Mlynarczuk J,Kotwica J.Influence of 4-hydroxylated polychlorinated biphenyls on the secretory function of bovine ovarian cells:Role of the steroidogenic factor-1receptor[J].Animal Reproduction Science,2015,155:89-98
- [60]杨旭光,郑伟娟,华子春.类固醇生成因子-1(SF-1)的研究进展[J].药物生物技术,2012,19(1):85-89Yang X G,Zheng W J,Hua Z C.Progress in the study of steroidogenic factor-1(SF-1)[J].Pharmaceutical Biotechnology,2012,19(1):85-89(in Chinese)
- [61]Yong E L,Hillier S G,Turner M,et al.Differential regulation of cholesterol side-chain cleavage(P450scc)and aromatase(P450arom)enzyme mRNA expression by gonadotrophins and cyclic AMP in human granulosa cells[J].Journal of Molecular Endocrinology,1994,12(2):239-249
- [62]Dickerson S M,Guevara E,Woller M J,et al.Cell death mechanisms in GT1-7 GnRH cells exposed to polychlorinated biphenyls PCB74,PCB118,and PCB153[J].Toxicology and Applied Pharmacology,2009,237(2):237-245
- [63]Berghuis S A,Soechitram S D,Sauer P J,et al.Prenatal exposure to polychlorinated biphenyls and their hydroxylated metabolites is associated with neurological functioning in 3-month-old infants[J].Toxicological Sciences,2014,142(2):455-462
- [64]Kuiper G G,Carlsson B,Grandien K,et al.Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta[J].Endocrinology,1997,138(3):863-870
- [65]Takeuchi S,Shiraishi F,Kitamura S,et al.Characterization of steroid hormone receptor activities in 100 hydroxylated polychlorinated biphenyls,including congeners identified in humans[J].Toxicology,2011,289(2):112-121
- [66]Nomiyama K,Hirakawa S,Eguchi A,et al.Toxicological assessment of polychlorinated biphenyls and their metabolites in the liver of Baikal seal(Pusa sibirica)[J].Environmental Science&Technology,2014,48(22):13530-13539
- [67]Kamata R,Shiraishi F,Nakajima D,et al.Mono-hydroxylated polychlorinated biphenyls are potent aryl hydrocarbon receptor ligands in recombinant yeast cells[J].Toxicology in Vitro,2009,23(4):736-743
- [68]汝少国,郭琳琳.环境污染物的抗雌激素效应及机制研究进展[J].科技导报,2015,33(9):93-99Ru S G,Guo L L.Research progress on antiestrogen effects and mechanism of environmental pollutants[J].Science&Technology Review,2015,33(9):93-99(in Chinese)
- [69]Ekuase E J,Liu Y,Lehmler H J,et al.Structure-activity relationships for hydroxylated polychlorinated biphenyls as inhibitors of the sulfation of dehydroepiandrosterone catalyzed by human hydroxysteroid sulfotransferase SULT2A1[J].Chemical Research in Toxicology,2011,24(10):1720-1728
- [70]刘碧旋,刘云岗.羟基多氯联苯对大鼠磺基转移酶1A1和2A3抑制作用的差异[J].毒理学杂志,2015,29(5):373-376