DNA adducts and P450 induction in human, rat and avian liver cells after exposure to polychlorobiphenyls

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Abstract

Polychlorinated biphenyls (PCBs) are industrial chemicals which have been detected in fish, birds and humans. They are known to exert marked effects on the liver. The induce hepatocellular carcinoma in rats and birds, and are suspected of being carcinogenic to humans. To better understand the genotoxic effects of PCBs, we used 32P-postlabelling to investigate DNA adduct formation, after exposure to PCBs (Aroclor 1254 and 3,′,4,4′-tetrachlorobiphenyl), in primary cultures of fetal hepatocytes from two animal species and in a human cell line (Hep G2). We also studied the induction of 7-ethoxyresorufin-O-deethylase (EROD) in these PCB-treated cells. The three cell types used are are known to express different cytochrome P450 families. The aim was to see whether a correlation could be established between EROD activity (a CYP1A1-related activity) and DNA adduct formation. DNA adducts were found in all three models after exposure to 50 μM 3,3′,4,4′-tetrachlorobiphenyl. The number of adducts was higher in quial hepatocytes (37 adducts per 109 nucleotides) than in rat hepatocytes or Hep G2 cells (20 adducts per 109 nucleotides in both cases). The major adduct was the same in all three cell types, but some adducts were found in only one or two species. These inter-species differences probably reflect metabolic differences leading to different ultimate carcinogens. Exposure to Aroclor 1254 failed to produce significant levels of DNA adduct, suggesting that pre-treated cells are required to magnify Aroclor 1254 metabolism. No correlation was found between adduct formation and the level of EROD induction.

References (51)

  • L. Roelandt et al.

    Effect of inducers and PCBs on the cyt P450 enzymes in culutured quail hepatocytes

    Ecotox. Environ. Safety

    (1995)
  • D.E. Ryan et al.

    Separation of characterization of highly purified forms of liver microsomal cytochrome P-450 from rats treated with polychlorinated biphenyls, phenobarbital and 3-methylcholantrene

    J. Biol. Chem.

    (1979)
  • S.H. Safe

    Polychlorinated biphenyls (PCBs): mutagenicity and carcinogenicity

    Mutation Res.

    (1989)
  • L. Sargent et al.

    In vitro chromosome damage due to PCB inteactions

    Mutation Res.

    (1989)
  • S. Sassa et al.

    Drug metabolism by the human hepatoma cell, Hep G2

    Biochem. Biophys. Res. Commun.

    (1987)
  • R.S. Schoeny et al.

    Non-mutagenicity for Salmonella of the chlorinated hydrocarbons aroclor 1254, 1,2,4-trichlorobenzene, MIREX and Kepone

    Mutation Res.

    (1979)
  • J.G. Vos

    Polychlorinated biphenyls as inducers of hepatic pophyria in Japonese quail, with special reference to δ-aminolevulinic acid synthetase activity fluorescence and residue in the livers

    Toxicol. Appl. Pharmacol.

    (1971)
  • A.P. Alvares et al.

    Polychlorinated biphenyls: a new type a inducer of cytochrome P448 in the liver

    Proc. Natl. Acad. Sci. USA

    (1973)
  • H. Brunn et al.

    Histology and histochemistry of the liver of chickens after chlorinated biphenyls

    Arch. Toxicol.

    (1987)
  • M.D. Burke et al.

    Ethoxyresorufin: direct fluormetric assay of a microsomal o-dealkylation which is preferentially inducible by 3-methylcholanthrene

    Drug Metab. Dispos.

    (1974)
  • K.J. Canters et al.

    Chemical threat to birds and mammals in the Netherlands

    Rev. Environ. Contam. Toxicol.

    (1993)
  • M. Dhouib et al.

    Liver and kidney DNA adducts formation and chlordane

    Toxicol. Lett.

    (1994)
  • Dubois M., De Wazier I., Thome J.P. and Kremers P. P450 induction by Aroclor 1254 and 3,3′,4,4′-tetrachlorobiphenyl in...
  • L. Ferrari et al.

    Differential effects of human recombinant interleukin-1β on cytochrome P-450 dependent activities in cultured fetan rat depatocytes

    Drug Metab. Dispos.

    (1992)
  • W.F. Greenlee et al.

    An improved assay 7-ethoxycoumarin-o-deethylase activity: induction of hepatic enzyme activity in c57BL/6J and DBA/2J mice by phenobarbital, 3-methylcholanthrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin

    J. Pharmac. Exp. Ther.

    (1978)
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