Skip to main content
Log in

Toxicokinetic interactions between chlorinated aromatic hydrocarbons in the liver of the C57BL/6J mouse: I. Polychlorinated biphenyls (PCBs)

  • Original Investigations
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

2,2′,4,4′,5,5′- (PCB 153), 2,3,3′,4,4′,5- (PCB 156) and 3,3′,4,4′,5,5′-hexachlorobiphenyl (PCB 169) were administered orally to three groups of C57BL/6J mice using single doses of 1.5–109.1 mg/kg. Two other groups of mice received binary mixtures of PCB 153 and 156 or PCB 153 and 169. The hepatic deposition, elimination, CYP1a and CYP2b dependent enzyme activities were studied during a 77-day period. Some interactive effects on hepatic deposition and elimination were observed, resulting in increased deposition and faster elimination. These effects were most pronounced for the PCBs 156 and 169. A potentiating effect on hepatic CYP1a dependent 7-ethoxyresorufin-O-deethylation (EROD) activity was observed for the combination of PCB 156 and 153. Based on the results from the present study and earlier studies, it is suggested that the potentiating effect on EROD activity might be caused by a mechanism that is governed by at least two factors. The first is a toxicokinetic modulation of hepatic retention. The second factor is probably an elevation of hepatic Ah receptor levels by PCB 153.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Abraham K, Krowke R, Neubert D (1988) Pharmacokinetics and biological activity of 2,3,7,8-tetrachlorodibenzo-dioxin: 1. Dose-dependent tissue distribution and induction of hepatic ethoxyresorufin-O-deethylase in rats following a single injection. Arch Toxicol 62: 359–368

    PubMed  Google Scholar 

  • Bannister R, Safe S (1987) Synergistic interactions of 2,3,7,8-TCDD and 2,2′,4,4′,5,5′-hexachlorobiphenyl in C57BL/6J and DBA/2J mice: role of the Ah receptor. Toxicology 44: 159–169

    PubMed  Google Scholar 

  • Biegel L, Harris M, Davis D, Rosengren R, Safe L, Safe S (1989) 2,2′,4,4′,5,5′-Hexachlorobiphenyl as a 2,3,7,8-tetrachlorodibenzo-p-dioxin antagonist in C57BL/6J mice. Toxicol Appl Pharmacol 97: 561–571

    PubMed  Google Scholar 

  • Birnbaum LS, Weber H, Harris MW, Lamb JC, McKinney JD (1985) Toxic increased incidence of cleft palate in mice. Toxicol Appl Pharmacol 77: 292–302

    PubMed  Google Scholar 

  • Curtis LR, Kerkvliet NI, Baecher-Steppan L, Carpenter HM (1990) 2,3,7,8-Tererachlorodibenzo-p-dioxin preteratment pf female mice altissue distribution but not hepatic metabolism of a subsequent dose. Fundam Appl Toxicol 14: 523–531

    PubMed  Google Scholar 

  • Davis D, Safe S (1990) Immunosuppressive activities of polychlorinated biphenyls in C57BL/6N mice: structure-activity relationships as Ah receptor agonists and partial antagonists. Toxicology 63: 97–111

    PubMed  Google Scholar 

  • De Jongh J, Wondergem F, Seinen W, Van den Berg M (1992) Absence of interactions on hepatic retention and 7-ethoxyresorufin-O-deethylation activity after co-administration of 1,2,3,7,8-pentachlorodibenzo-p-dioxin and 2,4,5,2′,4′,5′-hexachlorobiphenyl. Toxicology 75: 21–28

    PubMed  Google Scholar 

  • Denomme MA, Leece B, Li A, Towner R, Safe S (1986) Elevation of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) rat hepatic receptor by polychlorinated biphenyls. Structure-activity relationships. Biochem Pharmacol 35: 277–282

    PubMed  Google Scholar 

  • Dewailly E, Weber JP, Gingras S, Laliberté C (1991) Coplanar PCBs in human milk in the province of Québec, Canada: are they more toxic than dioxin for breast fed infants? Bull Environ Contam Toxicol 47: 491–498

    PubMed  Google Scholar 

  • Gulyaeva LF, Mishin VM, Lyakhovich VV (1986) Induction and catalytic activities of cytochromes P-450bb/e and P-450c in the liver microsomes of neonatal rats. Int J Biochem 18: 829–834

    PubMed  Google Scholar 

  • Hawker DW, Connell DW (1988) Octanol-water partition coefficients of polychlorinated biphenyl congeners. Environ Sci Technol 22: 382–387

    Google Scholar 

  • Hori S, Kashimoto T, Kunita N (1982) Effects of polychlorinated dibenzofuran on the retention of polychlorinated biphenyl isomers in the liver and adipose tissue of mice. J Food Hyg Soc Japan 23: 167–175

    Google Scholar 

  • Jensen AS (1987) Polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in human milk, blood and adipose tissue. Sci Tot Environ 64: 259–293

    Google Scholar 

  • Kannan N, Tanabe S, Tatsukawa R (1988) Toxic potential of non-ortho and mono-ortho coplanar PCBs in commercial PCB preparations: “2,3,7,8-T4CDD Toxicity Equivalence Factors Approach”. Bull Environ Contam Toxicol 41: 267–276

    PubMed  Google Scholar 

  • Kuroki J, Koga N, Yoshimura H (1986) High affinity of 2,3,4,7,8-pentachlorodibenzofuran to cytochrome P-450 in the hepatic microsomes of rats. Chemosphere 15: 731–738

    Google Scholar 

  • Lamparski LL, Nestrick TJ, Stehl RH (1979) Determination of part-per-Trillion concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin in fish. Anal Chem 51: 1453–1458

    PubMed  Google Scholar 

  • Langhorst MA, Shadoff LA (1980) Determination of part-per-trillion concentrations of tetra-, hexa-, hepta- and octachlorodibenzo-p-dioxins in human milk samples. Anal Chem 52: 2037–2044

    PubMed  Google Scholar 

  • Leece B, Denomme MA, Towner R, Li SMA, Safe S (1985) Polychlorinated biphenyls: correlation between in vivo and in vitro quantitative structure-activity relationships (QSARs). J Toxicol Environ Health 16: 379–388

    PubMed  Google Scholar 

  • Leece B, Denomme MA, Towner R, Li A, Landers J, Safe S (1987) Nonadditive interactive effects of polychlorinated biphenyl congeners in rats: role of the 2,3,7,8-tetrachlorodibenzo-p-dioxin receptor. Can J Physiol Pharmacol 65: 1908–1912

    PubMed  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with folin phenol reagent. J Biol Chem 193: 265–275

    PubMed  Google Scholar 

  • Lubet RA, Guengerich FP, Nims RW (1990) The induction of alkoxyresorufin metabolism: a potential indicator of environmental contamination. Arch Environ Contam Toxicol 19: 157–163

    PubMed  Google Scholar 

  • McKinley MK, Diliberto JJ, Birnbaum LS (1991) 2,3,7,8-Tetrachlorodibenzofuran (TCDF) pretreatment alters the hepatic metabolism of a subsequent dose. In: Dideriksen R, Hart B, Wills S (eds) Abstracts of the 11th International Symposium on Chlorinated Dioxins and Related Compounds, UNC, Chapel Hill, p 144

    Google Scholar 

  • Nebert D (1989) The Ah locus: genetic differences in toxicity, cancer, mutation, and birth defects. Crit Rev Toxicol 20: 153–174

    PubMed  Google Scholar 

  • Niimi AJ, Olivier BG (1989) Assessment of relative toxicity of chlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls in lake Ontario salmonids to mammalian systems using toxic equivalent factors (TEF). Chemosphere 18: 1413–1423

    Google Scholar 

  • Parkinson A, Safe S, Robertson LW, Thomas PE, Ryan DE, Reik LM, Levin W (1983) Immunochemical quantitation of cytochrome P-450 isoenzymes and epoxide hydrolase in liver microsomes from polychlorinated or polybrominated biphenyl-treated rats. J Biol Chem 258: 5967–5976

    PubMed  Google Scholar 

  • Poland A, Teitelbaum P, Glover E (1989) [125I]2-iodo-3,7,8-trichloro dibenzo-p-dioxin-binding species in mouse liver induced by agonists for the Ah receptor: characterization and identification. Mol Pharmacol 36: 113–120

    PubMed  Google Scholar 

  • Rappe C, Andersson R, Bergqvist PA, Brohede C, Hansson M, Kjeller LO, Lindström G, Marklund S, Nygren M, Swanson SE, Tysklind M, Wiberg K (1987) Overview on environmental fate of chlorinated dioxins and dibenzofurans. Sources, levels and isomeric pattern in various matrices. Chemosphere 16: 1603–1618

    Google Scholar 

  • Rutten AAJJL, Falke HE, Catsburg JF, Topp R, Blaauboer BJ, van Holsteijn I, Doorn L, van Leeuwen FXR (1987) Interlaboratory comparison of total cytochrome P-450 and protein determinations in rat liver microsomes. Arch Toxicol 61: 27–33

    PubMed  Google Scholar 

  • Ryan JJ, Lizotte R, Lau BPY (1985) Chlorinated dibenzo-p-dioxins and chlorinated dibenzofurans in Canadian human adipose tissue. Chemosphere 14: 697–706

    Google Scholar 

  • Safe S (1986) Comparative toxicology and mechanism of action of polychlorinated dibenzo-p-dioxins and dibenzofurans. Annu Rev Pharmacol Toxicol 26: 371–399

    PubMed  Google Scholar 

  • Safe S (1990) Polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and related compounds: mechanistic considerations which support the development of toxic equivalency factors (TEFs). Crit Rev Toxicol 21: 51–88

    PubMed  Google Scholar 

  • Schulz-Schalge T, Koch E, Schwind K, Hutzinger O, Neubert D (1990) Comparative study on the inductive potency of TCDD and TBrDD with three 2,3,7,8-mixed halogenated dioxins in liver microsomes of male rats. In: Hutzinger O, Fiedler H (eds) Proceedings of the 10th International Meeting on Dioxins and Organohalogen Compounds, vol 1, Eco-Informa Press, Bayreuth, pp 321–325

    Google Scholar 

  • Shen ES, Olson JR (1987) Relationship between the murine Ah phenotype and the hepatic uptake and metabolism of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Drug Metab Dispos 15: 653–660

    PubMed  Google Scholar 

  • Tanabe S, Kannan N, Subramanian A, Wantanabe S, Tatsukawa R (1987) Highly toxic coplanar PCBs: occurrence, source, persistency and toxic implications to wildlife and humans. Environ Pollut 47: 147–163

    PubMed  Google Scholar 

  • Voorman R, Aust SD (1989) TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) is a tight binding inhibitor of cytochrome P-450d. J Biochem Toxicol 4: 105–109

    PubMed  Google Scholar 

  • Yoshimura H, Yoshihara S, Koga N, Nagata K, Wada I, Kuroki J, Hokama Y (1985) Inductive effect on hepatic enzymes and toxicity of congeners of PCBs and PCDFs. Environ Health Perspect 59: 113–119

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

de Jongh, J., Wondergem, F., Seinen, W. et al. Toxicokinetic interactions between chlorinated aromatic hydrocarbons in the liver of the C57BL/6J mouse: I. Polychlorinated biphenyls (PCBs). Arch Toxicol 67, 453–460 (1993). https://doi.org/10.1007/BF01969915

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01969915

Key words

Navigation