多氯联苯暴露对实验鱼主要器官（组织）微细结构变化及几种酶活性的影响
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摘要
多氯联苯(Polychlorinated Biphenyls,PCBs)是一种人工合成的有机物，由于其性质稳定不易燃烧，绝缘性能优良，在工业上得到了广泛的应用。现在已造成了严重的环境污染。由于PCBs广泛存在于水环境中，在环境中难以降解，易于为生物吸收，并通过食物链在鱼类体内富集，从而对鱼类和人类造成了极大的危害。因而有必要对PCBs的鱼类毒性做深入的研究。
我们首先用0、50μg／L两个PCBs浓度，以浸浴法为斑马鱼染毒，经过28天的亚慢性毒性实验后，通过电镜观察受毒后斑马鱼肝脏和鳃组织的微细结构变化。随后，以0、2μd/L、50μg／L三个PCBs浓度为剑尾鱼染毒，测定72小时内肝、鳃及卵巢组织中的超氧化物歧化酶及Na~+／K~+—ATPase的活性变化。另外取对照组及50μg／L PCBs染毒组28天的剑尾鱼部分器官作组织超薄切片进行观察。实验还测定了PCBs对剑尾鱼成鱼30天的半致死浓度及对剑尾鱼幼鱼的96小时的半致死浓度。
实验中，斑马钱(BracAydanio rerlo)暴露在浓度为50μg／L PCBs的水中28天后，实验鱼的鳃丝外层上皮细胞细胞膜部分缺失或裂解，支持细胞核异形，氯细胞数目增多。肝脏细胞胞内溶酶体颗粒增多，有的见线粒体异常及细咆膜破裂，枯否氏细胞内吞噬物显著增加。
对剑尾鱼(Xiphophorus helleri)的亚慢性毒性实验，证实染毒后其
肝脏及鳃组织的透射电镜切片出现了明显的病理变化。肝细胞细胞核内
核仁明显，胞质内脂滴及溶酶体颗粒数量增多，粗面内质网增生且分布
靠近细胞膜，糖元颗粒减少，线粒体异常也有发现；鳃丝整体形态萎缩，
呼吸表皮细胞增厚，支持细胞细胞质内出现较多的染色颗粒，氯细胞有
所增加。肝脏及鳃的扫描电镜观察发现肝脏表面发现有部分细胞团明显
受损：部分鳃丝外表有损伤溃烂痕迹，鳃丝之间距离增宽。
对超氧化物歧化酶（Superoxide dismutase，SOD）的活性测定表明，
PCBS对剑尾鱼肝脏和卵巢的SOD活性有明显的影响。在最初染毒的
12小时内，SOD活性略有上升，但随暴露时间延长，浓度增加，肝和
卵巢的SOD活性均呈下降趋势。实验中鳃组织SOD活性在PCBS暴露
后其变化不明显。
对Na＋几丁－kxx－ase的活性测定表明，PCBs对剑尾鱼肝脏及卵巢的
Na丫K”－AThase活性有抑制作用但不显著，对鳃的Nd瓜＋－M ase活
性则显示有显著的抑制作用。
急性毒性实验表明，PCBs对剑尾鱼幼鱼96hr的半致死浓度（LC。）
为2．063ng／L，PCBS对剑尾鱼成鱼30天的半致死浓度为10．580be／L。
Polychlorinated Biphenyls (PCBs) are man-made organism. Due to it's stable quality, not easy to be fired and well insulative, PCBs has been used in industry widely. Now, PCBs contaminated the world badly especially in the water environment. Because PCBs is persistent and lipophilic, it was easily absorbed by creature, and enriched in the fishes by food chain. So, PCBs-exposure ubiquitous make the huge damage to fishes and mankind.
Zebrafish (Brachydanio rerio) were exposed to PCBs concentrations of ON 50ug/L for 4 weeks respectively. The gill and the liver morphology were examined by transmission eletron microslogy. Xiphophorus helleri were exposed to PCBs concentrations of (K 2ug/L> 50ug/L for 4 weeks, then revealed the pathological alteration by transmission eletron microslogy and scanning eletron microslogy. The activities of SOD and NaVK+桝TPase in 72 hi of swordtails(A7/?/2op/jorws /!e//en)were measured after the PCBs exposure respectively.The 30-day LCso of grown fish and 96 hr LCso of parr fish were measured after swordla\\s(Xiphophorus helleri)were exposed by PCBs.
With regard to zebrafish with PCBs-exposure, morphological
examination revealed that the membrane and partial cytoplasm of the epithelium cell in secondary lamella collapsed with lots of mucous and cell debris lying around. And the hepatocytes which exposed to PCBs for 4 weeks showed increase in the number of secondary lysosome, the phagocytosis of kupffer cell heightened.
The distinct pathological alteration occurred to swordtai\s(Xiphophorus helleri) which exposed to PCBs. Compared to the control groups, in the hepatocytes of exposed fishes, there were lots of lipid drops dispersive and lots of lipofuscin granule, on the same time, rough-surfaced endoplasmic reticulum hyperplasy abnormally, and some mitocondrium collapsed There were distinct alteration in gill filament and gill lamellae, the secondary lamella atrophy, and the supporting cells showed there were more secretion in cytoplasm.appeared abnormal, the abnormal nuclear also was found. The second lamellar and hepatocytes examined using scanning eletron microslogy revealed the second lamellar have damnification and canker. Because of the shrink of the secondary lamellar, the distance between two secondary lamellar broden. In the surface of liver, some injured hepatocyte can be found.
In this study, the result indicated that the activities of SOD in liver and ovary were influnced by PCBs remarkblely. There were a raise trend in the first 12 hr and then there are a down trend coupled with the extend of exposure time. However, the gill SOD activity was seldom be induced by PCBs. The gill Na+/K+-ATPase was inhibited by PCBs remarkably in PCBs-exposed groups. But the inhibitions to hepatic Na+/K"-ATPase and ovary Na+/K+-ATPase were not so remarkably.
56
When the swordtails (Xiphophorus helleri)exposed to PCBs, the 30-day LC50 of grown fish is 10.580ng/L and the 96 hr LCso of parr fish is 2.063ng/L.
我们首先用0、50μg／L两个PCBs浓度，以浸浴法为斑马鱼染毒，经过28天的亚慢性毒性实验后，通过电镜观察受毒后斑马鱼肝脏和鳃组织的微细结构变化。随后，以0、2μd/L、50μg／L三个PCBs浓度为剑尾鱼染毒，测定72小时内肝、鳃及卵巢组织中的超氧化物歧化酶及Na~+／K~+—ATPase的活性变化。另外取对照组及50μg／L PCBs染毒组28天的剑尾鱼部分器官作组织超薄切片进行观察。实验还测定了PCBs对剑尾鱼成鱼30天的半致死浓度及对剑尾鱼幼鱼的96小时的半致死浓度。
实验中，斑马钱(BracAydanio rerlo)暴露在浓度为50μg／L PCBs的水中28天后，实验鱼的鳃丝外层上皮细胞细胞膜部分缺失或裂解，支持细胞核异形，氯细胞数目增多。肝脏细胞胞内溶酶体颗粒增多，有的见线粒体异常及细咆膜破裂，枯否氏细胞内吞噬物显著增加。
对剑尾鱼(Xiphophorus helleri)的亚慢性毒性实验，证实染毒后其
肝脏及鳃组织的透射电镜切片出现了明显的病理变化。肝细胞细胞核内
核仁明显，胞质内脂滴及溶酶体颗粒数量增多，粗面内质网增生且分布
靠近细胞膜，糖元颗粒减少，线粒体异常也有发现；鳃丝整体形态萎缩，
呼吸表皮细胞增厚，支持细胞细胞质内出现较多的染色颗粒，氯细胞有
所增加。肝脏及鳃的扫描电镜观察发现肝脏表面发现有部分细胞团明显
受损：部分鳃丝外表有损伤溃烂痕迹，鳃丝之间距离增宽。
对超氧化物歧化酶（Superoxide dismutase，SOD）的活性测定表明，
PCBS对剑尾鱼肝脏和卵巢的SOD活性有明显的影响。在最初染毒的
12小时内，SOD活性略有上升，但随暴露时间延长，浓度增加，肝和
卵巢的SOD活性均呈下降趋势。实验中鳃组织SOD活性在PCBS暴露
后其变化不明显。
对Na＋几丁－kxx－ase的活性测定表明，PCBs对剑尾鱼肝脏及卵巢的
Na丫K”－AThase活性有抑制作用但不显著，对鳃的Nd瓜＋－M ase活
性则显示有显著的抑制作用。
急性毒性实验表明，PCBs对剑尾鱼幼鱼96hr的半致死浓度（LC。）
为2．063ng／L，PCBS对剑尾鱼成鱼30天的半致死浓度为10．580be／L。
Polychlorinated Biphenyls (PCBs) are man-made organism. Due to it's stable quality, not easy to be fired and well insulative, PCBs has been used in industry widely. Now, PCBs contaminated the world badly especially in the water environment. Because PCBs is persistent and lipophilic, it was easily absorbed by creature, and enriched in the fishes by food chain. So, PCBs-exposure ubiquitous make the huge damage to fishes and mankind.
Zebrafish (Brachydanio rerio) were exposed to PCBs concentrations of ON 50ug/L for 4 weeks respectively. The gill and the liver morphology were examined by transmission eletron microslogy. Xiphophorus helleri were exposed to PCBs concentrations of (K 2ug/L> 50ug/L for 4 weeks, then revealed the pathological alteration by transmission eletron microslogy and scanning eletron microslogy. The activities of SOD and NaVK+桝TPase in 72 hi of swordtails(A7/?/2op/jorws /!e//en)were measured after the PCBs exposure respectively.The 30-day LCso of grown fish and 96 hr LCso of parr fish were measured after swordla\\s(Xiphophorus helleri)were exposed by PCBs.
With regard to zebrafish with PCBs-exposure, morphological
examination revealed that the membrane and partial cytoplasm of the epithelium cell in secondary lamella collapsed with lots of mucous and cell debris lying around. And the hepatocytes which exposed to PCBs for 4 weeks showed increase in the number of secondary lysosome, the phagocytosis of kupffer cell heightened.
The distinct pathological alteration occurred to swordtai\s(Xiphophorus helleri) which exposed to PCBs. Compared to the control groups, in the hepatocytes of exposed fishes, there were lots of lipid drops dispersive and lots of lipofuscin granule, on the same time, rough-surfaced endoplasmic reticulum hyperplasy abnormally, and some mitocondrium collapsed There were distinct alteration in gill filament and gill lamellae, the secondary lamella atrophy, and the supporting cells showed there were more secretion in cytoplasm.appeared abnormal, the abnormal nuclear also was found. The second lamellar and hepatocytes examined using scanning eletron microslogy revealed the second lamellar have damnification and canker. Because of the shrink of the secondary lamellar, the distance between two secondary lamellar broden. In the surface of liver, some injured hepatocyte can be found.
In this study, the result indicated that the activities of SOD in liver and ovary were influnced by PCBs remarkblely. There were a raise trend in the first 12 hr and then there are a down trend coupled with the extend of exposure time. However, the gill SOD activity was seldom be induced by PCBs. The gill Na+/K+-ATPase was inhibited by PCBs remarkably in PCBs-exposed groups. But the inhibitions to hepatic Na+/K"-ATPase and ovary Na+/K+-ATPase were not so remarkably.
56
When the swordtails (Xiphophorus helleri)exposed to PCBs, the 30-day LC50 of grown fish is 10.580ng/L and the 96 hr LCso of parr fish is 2.063ng/L.
引文
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J.L. Hugla, J.P.Thome.1999． Effects of Polychlorinated Biphenyls on Liver Ultrastructure,Hepatic Monooxygenases, and Reproductive Success in the Barbel. Ecotoxicology and Environmental Safety. 42:265-273．
Jacob de Boer.Eh. 1994． 8-year study on the elimination of PCBs and other organochlorine comounds fron eel under nature conditions Environ Sci.Technol. 29 (13) :2242-2248．
Jamberg.U.,Asplund.L.,De Wit,et al. 1993． Polychlorinated biphenyls and polychlorinated naphthalenes in Swedish sediment and biota: Levels, patterns and time trends. Environ. Sci. Technol. 27:1364-1374．
Jones G.,Meyer U.A..1973． Morphological study of the liver lesion induce by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats. J.Pathol. 112:93-97．
Karas.P.,Neuman.E. and Sandstrom.O. 1991． Effects of pulp mill effluent on the population dynamics of perch.Perca fluviatilis. Can J .Fish.Aquat.Sci., 48:28-34．
Lars Forlin, Leif Norrgren. .1998． Physiological and Morphological Srudies of Feral Perch Before and After Remediation of a PCB Contaminated Lake:Jarnsjon. Ambio. 27(5) :418-423．
Larsson.A.,Haux.C.and Sjobeck M.L. 1985． Fish physiology and metal pollution:results and experiences from laboratory and field studies.Ecotox.Exviron.Safety . 9:250-281．
Larsson.P., Hamrin.S, Okla.L. 1991． Environ.Pollut.. 69:3950．
L.Karlsson-Norrgren, P.Runn, C.Haux, et al. 1985． Cadmium-induced changes in gill morphology of zebrafish, Brachydanio rerio (Hamilton-Buchanan), and rainbow trout, Salmo gairdneri Richardson. J.fish Biol. 27:81-95．
Lowry O.H.1951． Protein measurement with the Folin-Phenol reagent. J.Biol.Chem.l93:263-265．
Luksiene.D.and Sandstrom.O. 1994． Reproductive disturbance in a roach (Rutilus rutilus )population affected by cooling water discharge, J.Fish Biol. 45:613-625．
Lundholm C.E. 1988． The effects of DDE, PCB and chlordane on the binding of progesterone to its cytoplasmic receptor in the eggshell gland mucosa of birds and the endometrium of mammalian uterus. Comp.Biochem.Physiol. C89:361-368．
Monosson. E. and Stegeman J.J. 1991． Cytochrome P450E (P4501A) induction and inhibition in winter flounder by 3,3',4,4'-tetrachlorobiphenyl: comparison of response in fish from Georges Bank and Narragansett Bay. Environ. Toxicol. Chem. 10: 765-774．
Nilmi A.J. 1983． Biological and toxicological effects of environmental contaminants in fish and their eggs. Can.J.Fish.Aquat.Sci..40:306-312．
Norrgren L , Andersson T. ,Bjork M. 1993． Liver morphology and cytochrome P450 activity in fry of rainbow trout after microinjection of lipid-soluble xenobiotics in the yolk-sac embryos.Aquatic Toxicology . 2:307-316．
Omura T. and Sato R. 1964． The carbon monoxide-binding pigment of liver microsome. J.Biol.Chem. 239:2379-2385．
Orn.S., Andersson.P., Forlin.L.,Tysklind.M.and Norrgren.L. 1998． The impact on reproduction of an orally administered mixture of selected PCBs in zebrafish (Danio rerio). Arch.Environ.Contam.Toxicol.
Patxon R.and Limmiager B.L.1983． Altered activities of branchial and renal Na/K-and-Mg-ATPase in cold-acclimated goldfish(Carassius auratus).Comp.Biochem.Physiol.74B (3) : 503-506．
Peter L.D.,Livingstone D.R. 1996． Antioxdant enzyme activities in embryologic and early larval stages of turbot. J. Fish Biol. 49:96-997．
Poland A ,Knutson J.C. 1982． Anal. Rev. Pharmacol. Toxicol. 22:517-554．
Pulliainen.E.. Korhonen.K., Kankaanranta.L.and Maki.K. 1992． Non-spawning burbot on the northern coast of the Bothnian Bay. Ambio. 21:170-175．
Safe S. 1990 PCBs, PCDDsPCDFs and related compounds:Environmental and mechanistic considerations which support the development of toxic equivalency factors.CRC. Cril. Rev. Toxicol. 21:51-58．
Safe S. 1992． Environ Health Perspect. 100:259-268．
Safe S. 1993． Polychlorinated biphenyls-toxicology and risk assessment.
Organohalogen Compounds. 14:5358．
Safe S. 1994． Polychlorinated biphenyls(PCBs) : Environmental impact , biochemical and toxic responses , and implications for risk assessment. Crit.Rev.Toxicol. 24: 87-149．
Safe S.H. 1986． Anal. Rev. Pharmacol. Toxicol.26:371-399．
Sandstrom.O. 1994． Incomplete recovery in a coastal fish community exposed to effluent from a modernised Swedish bleached kraft mill. Can J .Fish.Aquat.Sci. 51:2215-2205．
Sandstrom.O.,Neuman.E. 1991． Pulp mill effluent effects on species distribution and recruitment in Baltic coastal fish. Finnish. Fish.Res. 12:101-110．
Sandstrom.O.,Neuman.E.and KarasP. 1988． Effects of a bleached pulp mill effluent on growth and gonad function in Baltic coastal fish, Water Sci.Technol. 20:107-118．
Schecter A.,Schaffner F., Tieman T. et al. 1984． Ultrastructural alterations of live mitochondria in response to dioxins, furans, PCBs and biphenykenes. In Biological Mechanism of Dioxin Action (A. Poland and R.D. Kimbrough, Eds),pp. 177-190, Vol.18． Branbury Report.
Schnellmann RG , et al . 1985． Metabolism and disposition of polychlorinated biphenyls In : Hodgson E, Bend JR, Philopt RM(eds). Reviews in biochemical toxicology.Amsterdam : Elsevier Press. 247-282．
Seegal RF., Bush B.1991． Brosch KO. Sub-chronic exposure of the adult rat to Aroclor1254 yields regionally-specific changes in central dopaminergic function. Neurotoxicology. 12:55-66．
Stouvenakers N., Hugla J.L., Goffiner G., Kremers P. and Thome J.P. 1996． Effects of PCBs on liver infrastructure and monooxygenase activities in Japanese quail. Bull.Environ.Contam.Toxicol. 56:839-846．
Wannermacher R., Rebstock A., Kulzer E., Schrenk D. and Bock K.W. 1992． Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on reproduction and oogenesis in zebrafish (Brachydanio rerio). Chemosphere . 24:1361-1368．
Weibel E.R., and Paumgartner D. 1978． Morphological changes associated with enzyme induction. In The Induction of Drug Metabolism (R.W.Estabrook and E.Lindenlaub, Eds.),pp. Schattauer Verlag. Stuttgart: 147-159．
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Wirgin. I.I., Kreamer.L., Grunwald. C., Squibb. K. and Gane. S.J. 1992． Effects of prior exposure history on cytochrome P4501A mRNA induction by PCB congener 77 in Atlantic tomcod, Mar. Environ. Res. 34: 103-108．
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GudrunBremLe, Lennart Okla and Per Larsson. 1995． Uptake of PCBs in fish in a contaminated river system: Bioconcentration factors measured in the field. Environ. Sci. Technol. 29: 2010-2015．
Haiber G. and Scholer H.F. 1994． 1dentification of Di-o,o-Cl-, mono-o-Cl-and non-o-Cl-substitued PCB congeners in Neckar river fish. Chemosphere. 28:1913-1919．
J.L. Hugla, G Goffinet., P. Kremers,et al.1996． Ultrastructural modifications in cultured fetal quail hepatocytes exposed to pesticides and PCBs.Ecotoxicology and Environmental Safety.34,145-155．
J.L. Hugla, J.P.Thome.1999． Effects of Polychlorinated Biphenyls on Liver Ultrastructure,Hepatic Monooxygenases, and Reproductive Success in the Barbel. Ecotoxicology and Environmental Safety. 42:265-273．
Jacob de Boer.Eh. 1994． 8-year study on the elimination of PCBs and other organochlorine comounds fron eel under nature conditions Environ Sci.Technol. 29 (13) :2242-2248．
Jamberg.U.,Asplund.L.,De Wit,et al. 1993． Polychlorinated biphenyls and polychlorinated naphthalenes in Swedish sediment and biota: Levels, patterns and time trends. Environ. Sci. Technol. 27:1364-1374．
Jones G.,Meyer U.A..1973． Morphological study of the liver lesion induce by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats. J.Pathol. 112:93-97．
Karas.P.,Neuman.E. and Sandstrom.O. 1991． Effects of pulp mill effluent on the population dynamics of perch.Perca fluviatilis. Can J .Fish.Aquat.Sci., 48:28-34．
Lars Forlin, Leif Norrgren. .1998． Physiological and Morphological Srudies of Feral Perch Before and After Remediation of a PCB Contaminated Lake:Jarnsjon. Ambio. 27(5) :418-423．
Larsson.A.,Haux.C.and Sjobeck M.L. 1985． Fish physiology and metal pollution:results and experiences from laboratory and field studies.Ecotox.Exviron.Safety . 9:250-281．
Larsson.P., Hamrin.S, Okla.L. 1991． Environ.Pollut.. 69:3950．
L.Karlsson-Norrgren, P.Runn, C.Haux, et al. 1985． Cadmium-induced changes in gill morphology of zebrafish, Brachydanio rerio (Hamilton-Buchanan), and rainbow trout, Salmo gairdneri Richardson. J.fish Biol. 27:81-95．
Lowry O.H.1951． Protein measurement with the Folin-Phenol reagent. J.Biol.Chem.l93:263-265．
Luksiene.D.and Sandstrom.O. 1994． Reproductive disturbance in a roach (Rutilus rutilus )population affected by cooling water discharge, J.Fish Biol. 45:613-625．
Lundholm C.E. 1988． The effects of DDE, PCB and chlordane on the binding of progesterone to its cytoplasmic receptor in the eggshell gland mucosa of birds and the endometrium of mammalian uterus. Comp.Biochem.Physiol. C89:361-368．
Monosson. E. and Stegeman J.J. 1991． Cytochrome P450E (P4501A) induction and inhibition in winter flounder by 3,3',4,4'-tetrachlorobiphenyl: comparison of response in fish from Georges Bank and Narragansett Bay. Environ. Toxicol. Chem. 10: 765-774．
Nilmi A.J. 1983． Biological and toxicological effects of environmental contaminants in fish and their eggs. Can.J.Fish.Aquat.Sci..40:306-312．
Norrgren L , Andersson T. ,Bjork M. 1993． Liver morphology and cytochrome P450 activity in fry of rainbow trout after microinjection of lipid-soluble xenobiotics in the yolk-sac embryos.Aquatic Toxicology . 2:307-316．
Omura T. and Sato R. 1964． The carbon monoxide-binding pigment of liver microsome. J.Biol.Chem. 239:2379-2385．
Orn.S., Andersson.P., Forlin.L.,Tysklind.M.and Norrgren.L. 1998． The impact on reproduction of an orally administered mixture of selected PCBs in zebrafish (Danio rerio). Arch.Environ.Contam.Toxicol.
Patxon R.and Limmiager B.L.1983． Altered activities of branchial and renal Na/K-and-Mg-ATPase in cold-acclimated goldfish(Carassius auratus).Comp.Biochem.Physiol.74B (3) : 503-506．
Peter L.D.,Livingstone D.R. 1996． Antioxdant enzyme activities in embryologic and early larval stages of turbot. J. Fish Biol. 49:96-997．
Poland A ,Knutson J.C. 1982． Anal. Rev. Pharmacol. Toxicol. 22:517-554．
Pulliainen.E.. Korhonen.K., Kankaanranta.L.and Maki.K. 1992． Non-spawning burbot on the northern coast of the Bothnian Bay. Ambio. 21:170-175．
Safe S. 1990 PCBs, PCDDsPCDFs and related compounds:Environmental and mechanistic considerations which support the development of toxic equivalency factors.CRC. Cril. Rev. Toxicol. 21:51-58．
Safe S. 1992． Environ Health Perspect. 100:259-268．
Safe S. 1993． Polychlorinated biphenyls-toxicology and risk assessment.
Organohalogen Compounds. 14:5358．
Safe S. 1994． Polychlorinated biphenyls(PCBs) : Environmental impact , biochemical and toxic responses , and implications for risk assessment. Crit.Rev.Toxicol. 24: 87-149．
Safe S.H. 1986． Anal. Rev. Pharmacol. Toxicol.26:371-399．
Sandstrom.O. 1994． Incomplete recovery in a coastal fish community exposed to effluent from a modernised Swedish bleached kraft mill. Can J .Fish.Aquat.Sci. 51:2215-2205．
Sandstrom.O.,Neuman.E. 1991． Pulp mill effluent effects on species distribution and recruitment in Baltic coastal fish. Finnish. Fish.Res. 12:101-110．
Sandstrom.O.,Neuman.E.and KarasP. 1988． Effects of a bleached pulp mill effluent on growth and gonad function in Baltic coastal fish, Water Sci.Technol. 20:107-118．
Schecter A.,Schaffner F., Tieman T. et al. 1984． Ultrastructural alterations of live mitochondria in response to dioxins, furans, PCBs and biphenykenes. In Biological Mechanism of Dioxin Action (A. Poland and R.D. Kimbrough, Eds),pp. 177-190, Vol.18． Branbury Report.
Schnellmann RG , et al . 1985． Metabolism and disposition of polychlorinated biphenyls In : Hodgson E, Bend JR, Philopt RM(eds). Reviews in biochemical toxicology.Amsterdam : Elsevier Press. 247-282．
Seegal RF., Bush B.1991． Brosch KO. Sub-chronic exposure of the adult rat to Aroclor1254 yields regionally-specific changes in central dopaminergic function. Neurotoxicology. 12:55-66．
Stouvenakers N., Hugla J.L., Goffiner G., Kremers P. and Thome J.P. 1996． Effects of PCBs on liver infrastructure and monooxygenase activities in Japanese quail. Bull.Environ.Contam.Toxicol. 56:839-846．
Wannermacher R., Rebstock A., Kulzer E., Schrenk D. and Bock K.W. 1992． Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on reproduction and oogenesis in zebrafish (Brachydanio rerio). Chemosphere . 24:1361-1368．
Weibel E.R., and Paumgartner D. 1978． Morphological changes associated with enzyme induction. In The Induction of Drug Metabolism (R.W.Estabrook and E.Lindenlaub, Eds.),pp. Schattauer Verlag. Stuttgart: 147-159．
Winston G.W.,Di Giulio R.T.1991． Prooxidant and antioxidant mechanisms in aquaic orgenism. Aquat. Toxicol..24:143-152．
Wirgin. I.I., Kreamer.L., Grunwald. C., Squibb. K. and Gane. S.J. 1992． Effects of prior exposure history on cytochrome P4501A mRNA induction by PCB congener 77 in Atlantic tomcod, Mar. Environ. Res. 34: 103-108．