Binding of a 3,3', 4,4'-tetrachlorobiphenyl (CB-77) metabolite to fetal transthyretin and effects on fetal thyroid hormone levels in mice.


:The present study was conducted in order to study the effect of the PCB congener 3,3', 4,4'-tetrachlorobiphenyl (CB-77) on fetal thyroxin homeostasis in the mouse, and to examine a possible underlying mechanism behind the effect. C57BL mice were treated with 14C-labelled or unlabelled CB-77 (1 or 10 mg/kg body wt.) on day 13 of gestation, and control animals were treated with corn oil. The experiment was terminated at 4 days after exposure. Maternal and fetal plasma and livers, and whole fetuses for homogenate preparation, were collected and analysed for total radioactivity, in vitro binding of 125I-thyroxin to plasma transthyretin (TTR; a thyroxin-transporting protein), and free and total thyroxin (FT4, TT4) levels. Maternal plasma, fetal plasma and homogenates were also analyzed for presence of CB-77 and metabolites. Results showed a dose-dependent uptake of radioactivity in plasma and liver, fetal plasma 14C-levels being about five-times higher in 10 mg/kg dosed animals as after 1 mg/kg. Fetal; plasma levels of total radioactivity were four- to nine-times above maternal levels and corresponded to only one compound, the metabolite 4-OH-3,3', 4',5-tetrachlorobiphenyl (4-OH-tCB). 4-OH-tCB was the major metabolite also in whole fetuses, with only small amounts of the parent compound (approximately 15% of the 4-OH-tCB) and traces (approximately 6%) of two other metabolites, 2-OH-3,3, 4,4'-tetrachlorobiphenyl and 5-OH-3,3', 4,4'-tetrachlorobiphenyl. Polyacrylamide gel electrophoresis confirmed that the 14C-radioactivity in fetal plasma was bound to TTR, and revealed that in vitro binding of 125I-T4 to fetal TTR was reduced to 50% of control values in treated animals (10 mg/kg body wt.). Fetal plasma FT4 and TT4 levels were significantly decreased (64 and 55% of control fetuses) after 10 mg/kg treatment. In conclusion, exposure of pregnant mice to CB-77 results in the accumulation of the metabolite 4-OH-tCB in fetal mouse plasma. The metabolite binds to TTR and is accompanied by a significant decrease in fetal plasma T4 levels. A causative correlation between TTR binding and effects on T4 levels is suggested.






Darnerud PO,Morse D,Klasson-Wehler E,Brouwer A




Has Abstract


1996-01-08 00:00:00














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    authors: Carmo H,Hengstler JG,de Boer D,Ringel M,Remião F,Carvalho F,Fernandes E,dos Reys LA,Oesch F,de Lourdes Bastos M

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  • Immunochemical detection of flucloxacillin adduct formation in livers of treated rats.

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    authors: Carey MA,van Pelt FN

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    authors: Rietjens IM,Van Bree L,Marra M,Poelen MC,Rombout PJ,Alink GM

    更新日期:1985-12-01 00:00:00

  • Diethyl 2-phenyl-2 tellurophenyl vinylphosphonate: an organotellurium compound with low toxicity.

    abstract::It is well-known that organotellurium compounds can have antioxidant activity in vitro, but in vivo these compounds can be potentially toxic to rodents. Here we investigated the potential in vitro and ex vivo toxicity of a new beta-organochalcogenyl vinylphosphonate, the diethyl 2-phenyl-2 tellurophenyl vinylphosphona...


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    authors: de Avila DS,Beque MC,Folmer V,Braga AL,Zeni G,Nogueira CW,Soares FA,Rocha JB

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  • Development of antidotes: problems and strategies.

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    pub_type: 杂志文章,评审


    authors: Szinicz L,Worek F,Thiermann H,Kehe K,Eckert S,Eyer P

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  • Toxicity of 2,3,7,8-tetrabromodibenzo-p-dioxin in rats after single oral administration.

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    pub_type: 杂志文章


    authors: Ivens IA,Löser E,Rinke M,Schmidt U,Neupert M

    更新日期:1992-01-01 00:00:00

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    pub_type: 杂志文章,评审


    authors: Doehmer J

    更新日期:1993-10-05 00:00:00

  • Effects of low concentrations of cadmium on immunoglobulin E production by human B lymphocytes in vitro.

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    authors: Jelovcan S,Gutschi A,Kleinhappl B,Sedlmayr P,Barth S,Marth E

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    authors: Ueng TH,Ueng YF,Tsai JN,Chao IC,Chen TL,Park SS,Iwasaki M,Guengerich FP

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  • Lung injury induced by trichloroethylene.

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    authors: Forkert PG,Sylvestre PL,Poland JS

    更新日期:1985-05-01 00:00:00

  • Studies on the induction of cholangiofibrosis by coumarin in the rat.

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    authors: Lawrence DA,Kim D

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  • Carcinogenicity of sodium dichromate and chromium (VI/III) oxide aerosols inhaled by male Wistar rats.

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    authors: Glaser U,Hochrainer D,Klöppel H,Oldiges H

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    authors: Vaas S,Kreft L,Schwarz M,Braeuning A

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    authors: Steffen C

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  • Cadmium induced ROS alters M1 and M3 receptors, leading to SN56 cholinergic neuronal loss, through AChE variants disruption.

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    pub_type: 杂志文章


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    pub_type: 杂志文章


    authors: Guo C,McMartin KE

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    pub_type: 杂志文章


    authors: Rodger I,Lam I,Purssell E,Thompson M,Rutter A,Ozolinš TR

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    pub_type: 杂志文章


    authors: Raja NS,Nair BU

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    pub_type: 杂志文章


    authors: Sharma P,Penney DG

    更新日期:1990-05-31 00:00:00