* School of Pharmaceutical Sciences, University of Shizuoka, 521, Yada, Shizuoka 422-8526, Japan;
Daiichi College of Pharmaceutical Sciences, 221, Tamagawa-cho, Minami-ku, Fukuoka 815-8511, Japan; and
Faculty of Nutritional Sciences, Nakamura Gakuen University, 571 Befu, Johnan-ku, Fukuoka 814-0198, Japan
Received September 30, 2002; accepted December 17, 2002
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ABSTRACT |
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Key Words: polychlorinated biphenyls; Kanechlor-500; thyroid hormones; UDP-glucuronosyltransferases; Wistar rats; ddy mice.
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INTRODUCTION |
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The worldwide commercial production of PCBs was banned in 1979, and yet, more than 70% of the global production of PCBs is estimated to be still in use or in stock (Hileman, 1993). Humans are continuously exposed to PCBs because of their presence in their accidental release from disposal sites (Phaneuf et al., 1995
) and in our diet, due in part to the accumulation of PCBs in certain species of fish and seafood collected in contaminated areas (Li and Hansen, 1997
). Despite their gradual decline, PCBs exist as major contaminants of human tissues (Newsome et al., 1995
).
Toxicities of PCBs (Safe, 1990; Brouwer et al., 1999
), such as body weight loss, endocrine disruption, impairments of reproductive and immune systems, teratogenicity, and carcinogenicity, have been intensively studied over the last 30 years. Spectra of the toxicities are different between the species of animals (McConnell, 1989
; Safe, 1994
), and the species difference is believed to occur through the difference in their metabolism of PCBs (Duignan et al., 1987
, 1988
). Decreases in serum thyroid hormones in rats by PCBs such as 3,3',4,4',5-pentachlorobiphenyl (3,3',4,4',5-pentaCB), Aroclor 1254, and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (Barter and Klaassen, 1994
; Schuur et al., 1997
; Van Birgelen et al., 1995
) have been reported, and the decrease is thought to occur through PCB-mediated induction of hepatic UDP-glucuronosyltransferases (UDP-GTs), especially UGT1A1 and UGT1A6 (Visser, 1996
). Likewise, some PCB congeners such as 2,3',4,4',5- and 3,3',4,4',5-pentaCBs and 2,2',4,4',5,5'- and 2,3,3',4,4',5-hexachlorobiphenyls (2,2',4,4',5,5'- and 2,3,3',4,4',5-hexaCBs) are reported to decrease the level of serum thyroid hormones and to increase the activity of hepatic drug-metabolizing enzymes in rats (Ness et al., 1993
; Van Birgelen et al., 1995
). We have also reported that nonplanar PCBs such as 2,2',4,5,5'-pentaCB and 2,2',3,3',4,6'-hexaCB decrease the level of serum total thyroxine (T4) in both rats and mice (Kato et al., 2001
). More recently, Craft et al. (2002)
have reported that TCDD-like and phenobarbital-like PCB congeners induce hypothyroxinemia in both rats and mice through induction of hepatic UDP-GTs and that there is a species difference in magnitude of decrease in serum thyroid hormone level, and the difference is attributed to that in the increase of hepatic UDP-GTs. To date, however, only limited data are available on the species difference in the altered level of serum thyroid hormone by PCBs.
In the present study, we examined the species differences between rats and mice in altered levels of drug-metabolizing enzyme and serum thyroid hormone by Kanechlor-500, a commercial PCB mixture.
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MATERIALS AND METHODS |
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Animal treatments.
Male Wistar rats, weighing 160200 g, and male ddy mice, weighing 2836 g, were housed, three or four per cage, with free access to commercial chow and tap water, and maintained on a 12-h dark/light cycle (8:00 A.M.-8:00 P.M. light) in an air-controlled room (temperature: 24.5 ± 1°C, humidity: 55 ± 5%). Rats and mice received a single ip injection of KC500 (100 mg/kg body weight) dissolved in Panacete 810 (5 ml/kg). Control animals were treated with vehicle alone (5 ml/kg).
Analysis of serum hormones.
All animals used were killed by decapitation on day 4 after the dosing, and the thyroid gland and liver were removed and weighed. Blood was collected from each animal between 10:30 and 11:30 A.M. After clotting at room temperature, serum was separated by centrifugation and stored at -50°C until used. Levels of total T4, total triiodothyronine (T3), and thyroid-stimulating hormone (TSH) were measured by radioimmunoassays using Amerlex-MT4, Amerlex-MT3 (Ortho-Clinical Diagnostics Co.; Amersham, UK), and Biotrak rTSH [125I] assay system (Amersham Life Science, Ltd.; Little Chalfont, UK), respectively.
Hepatic microsomal enzyme assays.
Hepatic microsomes were prepared according to the method as described previously (Kato et al., 1995a). The protein content was determined by the method of Lowry et al. (1951)
with bovine serum albumin as a standard. Amount of microsomal cytochrome P450 (P450) was estimated according to the method of Omura and Sato (1964)
. Microsomal O-dealkylase activities of 7-benzyloxy-, 7-ethoxy-, and 7-pentoxy-resorufins were determined by the method of Burke et al. (1985)
. The activities of microsomal UDP-GT toward T4, 4-nitrophenol, and chloramphenicol were determined by the methods of Barter and Klaassen (1992), Isselbacher et al. (1962)
and Ishii et al. (1994)
, respectively. In addition, all UGP-GT activities were measured after activation of UDP-GT by 0.05% Brij 58.
RT-PCR analysis for gene expression of UGT1A1 and UGT1A6.
Total hepatic RNAs were prepared with ISOGEN (NipponGene, Japan) and used for the determination of the gene expression of UDP-GT isoforms, UGT1A1 and UGT1A6, and ribosomal protein L27a (RPL27), an internal control. A portion (4 µg) of total RNA was converted to cDNA by use of poly d(N)6 primer (Pharmacia Biotech) and Moloney murine leukemia virus reverse transcriptase (GIBCO, BRL) in an RT-reaction mixture (20 µl). PCR was performed in a total reaction mixture (25 µl) containing 0.8 µl of the RT-reaction mixture, 0.5 µl of each primer set and AmpliTaq Gold DNA polymerase (Perkin Elmer). The primer sets used were as follows: rat UGT1A1 (Kasahara et al., 2002), 5'-TGGTGTGCCGGAGCTCATGTTCG-3' (forward) and 5'-ACTCCGCCCAAGTTCCACAAAAGCA-3' (reverse); rat UGT1A6 (Kasahara et al., 2002
), 5'-TGCTCGACTTCCTGCAGGTTTC-3' (forward) and 5'-TTCCTGTACTCTCTTAGAGGAGCCA-3' (reverse); mouse UGT1A1 (Bernard et al., 1999
), 5'-CAGGTTTCTCCTCGTGTGTC-3' (forward) and 5'-CATACTGGAATCCCTTTTGA-3' (reverse); mouse UTG1A6, 5'-TCAGACACTTCCTGCAGGGTTTC-3' (forward) and 5'-TTCCTGTACTCTCTTAGAGGACCCA-3' (reverse). Amplifications of all cDNA examined were performed with GeneAmp PCR System 9700 (PE Applied Biosystems, Foster, Calif., USA). The PCR program used for the analyses of UGT1A1 and UGT1A6 in rats and mice was as follows: pretreatment, at 94°C for 2 min; denaturation at 94°C for 20 s; annealing, at 57°C for 45 s; extension, at 72°C for 45 s; and chase reaction, at 72°C for 10 min. Each PCR product was separated by electrophoresis on a 2% agarose gel and the separated PCR product was visualized by ethidium bromide staining under ultraviolet light. The predicted size of each PCR product is as follows: rat UGT1A1 and UGT1A6 (Kasahara et al., 2002
), 290 and 300 base pairs (bp), respectively; mouse UGT1A1 (Bernard et al., 1999
) and UGT1A6, 442 and 318 bp, respectively. In addition, PCR for the RPL27 in rats and mice (Wool et al., 1990
), an internal standard, was performed with a primer set: 5'-ATCGGTAAGCACCGCAAGCA-3' (forward) and 5'-GGGAGCAACTCCATTATTGT-3' (reverse) for both rats and mice, and the predicted product size is 234 bp.
Determination of MeSO2 metabolites from KC500 in the liver.
Amounts of MeSO2-PCBs in the liver were determined with GC/MS (Mimura et al., 1999). M+ and M+2 for MeSO2-tetraCB (m/z 368 and 370, respectively), MeSO2-pentaCB (m/z 402 and 404, respectively), and MeSO2-hexaCB (m/z 436 and 438, respectively) were monitored as selected ions.
Statistics.
The data obtained were statistically analyzed according to Students t-test.
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RESULTS |
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In both species of rats and mice, KC500-treatment resulted in significant increase in the liver weight: 1.4- and 1.1-fold, respectively (Table 1). Likewise, the treatment resulted in significant increases in hepatic microsomal enzymes in rats and mice; P450 content: 3.2- and 1.2-fold, respectively; benzyloxyresorufin O-dealkylase activity (CYP2B and CYP3A): 86- and 10.2-fold, respectively; pentoxyresorufin O-dealkylase activity (CYP2B): 25- and 7.3-fold, respectively; ethoxyresorufin O-dealkylase activity (CYP1A): 46- and 1.9-fold, respectively (Table 2
). Furthermore, KC500-treatment led to significant increases in UDP-GT activities toward T4 and 4-nitrophenol in rats but not in mice (Table 3
). UDP-GT activity toward chloramphenicol was extensively increased in rats and slightly in mice.
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DISCUSSION |
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In general, the decrease in serum T4 level by PCB congeners such as 3,3',4,4'-tetraCB, 2,3',4,4',5'-pentaCB, 2,3,3',4,4',5- and 2,2',4,4',5,5'-hexaCBs and Aroclor 1254 have been reported to decrease serum thyroid hormone levels in rats (Barter and Klaassen, 1994; Liu et al., 1995
; Ness et al., 1993
; Van Birgelen et al., 1995
). This has been thought to occur through induction of T4-UDP-GTs (Schuur et al., 1997
; Van Birgelen et al., 1995
; Visser, 1996
). Our preliminary study (Kato et al., 2002
), however, indicated that the activity of T4-UDP-GT was significantly increased in Wistar rats, but not in UGT1A-deficient Gunn rats, by KC500 treatment, although serum total T4 levels in both strains of rat were significantly reduced by the treatment. This suggests strongly that the decrease in serum total T4 levels in not only mice but also rats by PCBs would not be induced only through increase in hepatic T4 glucuronidation. PCB congeners (Chauhan et al., 2000
) and their hydroxylated metabolites (Brouwer et al., 1998
; Lans et al., 1993
) show in vitro binding to transthyretin (TTR), a major thyroid hormone transporting protein, which plays an essential role in the homeostasis of T4 (Schreiber et al., 1995
), suggesting that decrease in the level of serum T4 in KC500-treated mice and rats might occur, at least in part, through a TTR-associated pathway.
To determine the mechanism for decrease in the serum T3 level in KC500-treated mice, we examined KC500-altered levels of hepatic microsomal UGT2B2 enzyme by Western blotting with antirat UGT2B polyclonal antibody, because T3 glucuronidation is efficiently mediated by UGT2B2 enzyme (van Raaij et al., 1993; Visser et al., 1993
). UGT2B2, however, was not detected in any experimental group of rats or mice, although other UGT2B subfamily enzymes (UGT2B3, UGT2B6, and UGT2B12) were detected in all the experimental groups examined (data not shown). Accordingly, the decrease in serum T3 levels in mice by KC500 seems to occur without increase in the UGT2B2.
As a possible mechanism for the decrease in the levels of serum T4 and T3, increase in estrogen sulfotransferase, which efficiently catalyzes the sulfation of iodothyronines T4 and T3 (Kester et al., 1999), might be considered. However, since Aroclor 1254 has been reported to show only a minimal impact on overall outer ring deiodination activity (Hood and Klaassen, 2000
), KC500 seems to hardly induce deiodinases converting T4 to T3. Furthermore, we showed in the present study that serum TSH levels in either rats or mice was not significantly changed by KC500, indicating that TSH is not attributed to a decrease in serum T4 and/or T3 levels by KC500. In addition, it had been reported that serum TSH level was little affected by PCBs (Hallgren et al., 2001
; Hood et al., 1999
; Liu et al., 1995
).
We have previously reported that 3-MeSO2 metabolites of nonplanar PCBs have definite activities for inducing hepatic microsomal drug-metabolizing enzymes, and their activities were much greater than parent PCBs (Kato et al., 1995a,b
, 1999b
). We further demonstrated that 3-MeSO2-2,3',4',5-tetraCB, 3-MeSO2-2,2',3',4',5-pentaCB, 3-MeSO2-2,2',4',5,5'-pentaCB, 4-MeSO2-2,2',4',5,5'-pentaCB, 3-MeSO2-2,2',3',4',5,6-hexaCB, 3-MeSO2-2,2',4',5,5',6-hexaCB and 4-MeSO2-2,2',4',5,5',6-hexaCB could reduce serum T4 level (Kato et al., 1998
, 1999a
). KC500, used in the present study, includes many nonplanar PCBs which were biotransformed to MeSO2 metabolites, thus posing the possibility that MeSO2-PCB metabolites formed are attributed to decrease in the level of serum thyroid hormones in KC500-treated rats and mice. However, species difference between rats and mice in induced levels of hepatic drug-metabolizing enzymes was not necessarily correlated with that in the decreased level of serum thyroid hormones. Although hepatic concentrations of MeSO2-PCB metabolites in KC500-treated mice were much higher than those in KC500-treated rats, the decreased levels in serum T4 in rats and mice were almost the same. Furthermore, the magnitude of the induction of T4-UDP-GT and cytochrome P450 enzymes was greater in rats than in mice, despite hepatic levels of MeSO2 metabolites being greater in mice than in rats. Namely, the difference between rats and mice in the level of MeSO2 metabolites was not correlated with the difference in induction of microsomal drug-metabolizing enzymes or in reduction of serum thyroid hormone.
In conclusion, we demonstrate for the first time that in mice, the decrease in serum T4 level by KC500 occurs without increase in the T4-UDP-GTs, UGT1A1, and UGT1A6 responsible for glucuronidation of T4, and further suggest that the decrease in rats would not be produced only through induction of the T4-UDP-GTs. However, exact mechanisms for KC500-mediated decrease in serum thyroid hormone levels in rats and mice remain unclear, and further studies are necessary for understanding the susceptibility to PCBs in animals including humans.
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ACKNOWLEDGMENTS |
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NOTES |
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REFERENCES |
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Barter, R. A., and Klaassen, C. D. (1994). Reduction of thyroid hormone levels and alteration of thyroid function by four representative UDP-glucuronosyltransferase inducers in rats. Toxicol. Appl. Pharmacol. 128, 917.[CrossRef][ISI][Medline]
Bernard, P., Goudonnet, H., Artur, Y., Desvergne, B., and Wahli, W. (1999). Activation of the mouse TATA-less and human TATA-containing UDP-glucuronosyltransferase 1A1 promoters by hepatocyte nuclear factor 1. Mol. Pharmacol. 56, 526536.
Brouwer, A., Longnecker, M. P., Birnbaum, L. S., Cogliano, J., Kostyniak, P., Moore, J., Schantz, S., and Winneke, G. (1999). Characterization of potential endocrine-related health effects at low-dose levels of exposure to PCBs. Environ. Health Perspect. 107, 639649.[ISI][Medline]
Brouwer, A., Morse, D. C., Lans, M. C., Schuur, A. G., Murk, A. J., Klasson-Wehler, E., Bergman, Å., and Visser, T. J. (1998). Interactions of persistent environmental organohalogens with the thyroid hormone system: Mechanisms and possible consequences for animal and human health. Toxicol. Ind. Health 14, 5984.[ISI][Medline]
Burke, M. D., Thompson, S., Elcombe, C. R., Halpert, J., Haaparanta, T., and Mayer, R. T. (1985). Ethoxy-, pentoxy-, and benzyloxyphenoxazones and homologues: A series of substrates to distinguish between different induced cytochromes P-450. Biochem. Pharmacol. 34, 33373345.[CrossRef][ISI][Medline]
Chauhan, K. R., Kodavanti, P. R. S., and McKinney, J. D. (2000). Assessing the role of ortho-substitution on polychlorinated biphenyl binding to transthyretin, a thyroxine transport protein. Toxicol. Appl. Pharmacol. 162, 1021.[CrossRef][ISI][Medline]
Craft, E. S., DeVito, M. J., and Crofton, K. M. (2002). Comparative responsiveness of hypothyroxinemia and hepatic enzyme induction in Long-Evans rats versus C57BL/6J mice exposed to TCDD-like and phenobarbital-like polychlorinated biphenyl congeners. Toxicol. Sci. 68, 372380.
Duignan, D. B., Sipes, I. G., Ciaccio, P. J., and Halpert, J. R. (1988). The metabolism of xenobiotics and endogenous compounds by the constitutive dog liver cytochrome P450 PBD-2. Arch. Biochem. Biophys. 267, 294304.[ISI][Medline]
Duignan, D. B., Sipes, I. G., Leonard, T. B., and Halpert, J. R. (1987). Purification and characterization of the dog hepatic cytochrome P450 isozyme responsible for the metabolism of 2,2',4,4',5,5'-hexachlorobiphenyl. Arch. Biochem. Biophys. 255, 290303.[ISI][Medline]
Hallgren, S., Sinjari, T., Håkansson, H., and Darnerud, P. O. (2001). Effects of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) on thyroid hormone and vitamin A levels in rats and mice. Arch. Toxicol. 75, 200208.[CrossRef][ISI][Medline]
Haraguchi, K., Kuroki, H., and Masuda, Y. (1987). Synthesis and characterization of tissue-retainable methylsulfonyl polychlorinated biphenyl isomers. J. Agric. Food Chem. 35, 178182.[ISI]
Hileman, B. (1993). Concerns broaden over chlorine and chlorinated hydrocarbons. Chem. Eng. News April 19, 1120.
Hood, A., Hashmi, R., and Klaassen, C. D. (1999). Effects of microsomal enzyme inducers on thyroid-follicular cell proliferation, hyperplasia, and hypertrophy. Toxicol. Appl. Pharmacol. 160, 163170.[CrossRef][ISI][Medline]
Hood, A., and Klaassen, C. D. (2000). Effects of microsomal enzyme inducers on outer-ring deiodinase activity toward thyroid hormones in various rat tissues. Toxicol. Appl. Pharmacol. 163, 240248.[CrossRef][ISI][Medline]
Ishii, Y., Tsuruda, K., Tanaka, M., and Oguri, K. (1994). Purification of a phenobarbital-inducible morphine UDP-glucuronyltransferase isoform, absent from Gunn rat liver. Arch. Biochem. Biophys. 315, 345351.[CrossRef][ISI][Medline]
Isselbacher, K. J., Chrabas, M. F., and Quinn, R. C. (1962). The solubilization and partial purification of a glucuronyl transferase from rabbit liver microsomes. J. Biol. Chem. 237, 30333036.
Kasahara, T., Hashiba, M., Harada, T., and Degawa, M. (2002). Change in the gene expression of hepatic tamoxifen-metabolizing enzymes during the process of tamoxifen-induced hepatocarcinogenesis in female rats. Carcinogenesis 23, 491498.
Kato, Y., Haraguchi, K., Kawashima, M., Yamada, S., Masuda, Y., and Kimura, R. (1995a). Induction of hepatic microsomal drug-metabolizing enzymes by methylsulphonyl metabolites of polychlorinated biphenyl congeners in rats. Chem. Biol. Interact. 95, 257268.[CrossRef][ISI][Medline]
Kato, Y., Haraguchi, K., Kawashima, M., Yamada, S., Isogai, M., Masuda, Y., and Kimura, R. (1995b). Characterization of hepatic microsomal cytochrome P-450 from rats treated with methylsulphonyl metabolites of polychlorinated biphenyl congeners. Chem. Biol. Interact. 95, 269278.[CrossRef][ISI][Medline]
Kato, Y., Haraguchi, K., Shibahara, T., Masuda, Y., and Kimura, R. (1998). Reduction of thyroid hormone levels by methylsulfonyl metabolites of polychlorinated biphenyl congeners in rats. Arch. Toxicol. 72, 541544.[CrossRef][ISI][Medline]
Kato, Y., Haraguchi, K., Shibahara, T., Yumoto, S., Masuda, Y., and Kimura, R. (1999a). Reduction of thyroid hormone levels by methylsulfonyl metabolites of tetra- and pentachlorinated biphenyls in male Sprague-Dawley rats. Toxicol. Sci. 48, 5154.
Kato, Y., Haraguchi, K., Tomiyasu, K., Saito, H., Shibahara, T., Masuda, Y., and Kimura, R. (1999b) The role of 3-methylsulfonyl-2,2',4',5,5'-pentachlorobiphenyl, a metabolite of 2,2',4,5,5'-pentachlorobiphenyl, in the induction of hepatic microsomal drug-metabolizing enzymes by 2,2',4,5,5'-pentachlorobiphenyl in rats. Environ. Toxicol. Pharmacol. 8, 3947.[CrossRef][ISI]
Kato, Y., Yamazaki, T., Haraguchi, K., Ito, Y., Nemoto, K., Masuda, Y., Degawa, M., and Kimura, R. (2001). Effects of 2,2',4,5,5'-pentachlorobiphenyl and 2,2',3,3',4,6'-hexachlorobiphenyl on serum hormone levels in rats and mice. Organohalogen Compd. 53, 4446.
Kato, Y., Yamazaki, T., Ikushiro, S., Ito, Y., Haraguchi, K., Iyanagi, T., Kimura R., and Degawa, M. (2002). Relation between the increase in hepatic UDP-glucuronosyltransferase and the decrease in serum thyroxine level in Kanechlor-500-treated rats. Organohalogen Compd. 56, 8587.
Kester, M. H. A., Van Dijk, C. H., Tibboel, D., Hood, A. M., Rose, N. J. M., Meinl, W., Pabel, U., Glatt, H., Falany, C. N., Coughtrie, M. W. H, and Visser, T. .J. (1999). Sulfation of thyroid hormone by estrogen sulfotransferase. J. Clin. Endocrinol. Metab. 84, 25772580.
Kuratsune, M., Yoshimura, H., Matsuzaka, J., and Yamaguchi, A. (1972). Epidemiologic study on Yusho, a poisoning caused by ingestion of rice oil contaminated with a commercial brand of polychlorinated biphenyls. Environ. Health Perspect. 46, 119128.
Lans, M. C., Klasson-Wehler, E., Willemsen, M., Meussen, E., Safe, S., and Brouwer, A. (1993). Structure-dependent, competitive interaction of hydroxy-polychlorobiphenyls, -dibenzo-p-dioxins, and -dibenzofurans with human transthyretin. Chem. Biol. Interact. 88, 721.[CrossRef][ISI][Medline]
Li, M.-H., and Hansen, L. G. (1997). Consideration of enzyme and endocrine interactions in the risk assessment of PCBs. Rev. Toxicol. 1, 71156.
Liu, J., Liu, Y., Barter, R. A., and Klaassen, C. D. (1995). Alteration of thyroid homeostasis by UDP-glucuronosyltransferase inducers in rats: A dose-response study. J. Pharmacol. Exp. Ther. 273, 977985.[Abstract]
Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193, 265275.
McConnell, E. E. (1989). In halogenated biphenyls, terphenyls, naphthalenes, dibenzodioxins, and related products (R.D. Kimbrough and A.A. Jensen, Eds.), pp. 161193. Elsevier, Amsterdam.
Mimura, K., Tamura, M., Haraguchi, K., and Masuda, Y. (1999). Analysis of 209 PCB congeners by high separation gas chromatography/low resolution mass spectrometer. Fukuoka Acta Med. 90, 192201.[Medline]
Ness, D. K., Schantz, S. L., Moshtaghian, J., and Hansen, L. G. (1993). Effects of perinatal exposure to specific PCB congeners on thyroid hormone concentrations and thyroid histology in the rat. Toxicol. Lett. 68, 311323.[CrossRef][ISI][Medline]
Newsome, H. W., Davies, D., and Doucet, J. (1995). PCB and organochlorine pesticides in Canadian human milk - 1992. Chemosphere 30, 21432153.[CrossRef][ISI][Medline]
Omura, T., and Sato, R. (1964). The carbon monoxide-binding pigment of liver microsomes: I. Evidence for its hemoprotein nature. J. Biol. Chem. 239, 23702378.
Phaneuf, D., DesGranges, J. L., Plante, N., and Rodrigue, J. (1995). Contamination of local wildlife following a fire at a polychlorinated biphenyl warehouse in St. Basile le Grand, Quebec, Canada. Arch. Environ. Contam. Toxicol. 28, 145153.[ISI][Medline]
Safe, S. H. (1990). Polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and related compounds: Environmental and mechanistic considerations that support the development of toxic equivalency factors (TEFs). Crit. Rev. Toxicol. 21, 5188.[ISI][Medline]
Safe, S. H. (1994). Polychlorinated biphenyls (PCBs): Environmental impact, biochemical and toxic responses, and implications for risk assessment. Crit. Rev. Toxicol. 24, 87149.[ISI][Medline]
Schuur, A. G., Boekhorst, F. M., Brouwer, A., and Visser, T. J. (1997). Extrathyroidal effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on thyroid hormone turnover in male Sprague-Dawley rats. Endocrinology 138, 37273734.
Schreiber, G., Southwell, B. R., and Richardson, S. J. (1995). Hormone delivery systems to the brain-transthyretin. Exp. Clin. Endocrinol. 103, 7580.[ISI]
Shimada, T., Nunoura, Y., Kitanaka, E., Iwagami, S., and Mizuta, Y. (1976). Induction of mouse and rat liver microsomal enzymes by polychlorinated biphenyls in relation to the PCB levels in tissue. Folia Pharmacol. Japon. 72, 955967.[ISI]
van Birgelen, A. P. J. M., Smit, E. A., Kampen, I. M., Groeneveld, C. N., Fase, K. M., van der Kolk, J., Poiger, H., van den Berg, M., Koeman, J. H., and Brouwer, A. (1995). Subchronic effects of 2,3,7,8-TCDD or PCBs on thyroid hormone metabolism: Use in risk assessment. Eur. J. Pharmacol. 293, 7785.[Medline]
van Raaij, J. A., Kaptein, E., Visser, T. J., and van den Berg, K. J. (1993). Increased glucuronidation of thyroid hormone in hexachlorobenzene-treated rats. Biochem. Pharmacol. 45, 627631.[CrossRef][ISI][Medline]
Visser, T. J. (1996). Pathways of thyroid hormone metabolism. Acta Med. Austriaca Heft 1/2, 1016.
Visser, T. J., Kaptein, E., van Raaij, J. A., Joe, C. T., Ebner, T., and Burchell, B. (1993). Multiple UDP-glucuronyltransferases for the glucuronidation of thyroid hormone with preference for 3,3',5'-triiodothyronine (reverse T3). FEBS Lett. 315, 6568.[CrossRef][ISI][Medline]
Viollon-Abadie, C., Lassere, D., Debruyne, E., Nicod, L., Carmichael, N., and Richert, L. (1999). Phenobarbital, ß-naphthoflavone, clofibrate, and pregnenolone-16-carbonitrile do not affect hepatic thyroid hormone UDP-glucuronosyl transferase activity, and thyroid gland function in mice. Toxicol. Appl. Pharmacol. 155, 112.[CrossRef][ISI][Medline]
Wool, I. G., Chan, Y. L., Paz, V., and Olvera, J. (1990). The primary structure of rat ribosomal proteins: The amino acid sequences of L27a and L28 and corrections in the sequence of S4 and S12. Biochim. Biophys. Acta 1050, 6973.[ISI][Medline]