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

doi:10.1016/0165-1218(95)90053-5

Mutation Research/Genetic Toxicology

Volume 345, Issues 3–4, December 1995, Pages 181-190

https://doi.org/10.1016/0165-1218(95)90053-5 Get rights and content

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.

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

Abstract

Eur. J. Pharmacol.

J. Chromatogr.

Cell Differ.

Comp. Biochem. Physiol.

J. Biol. Chem.

Chem. Biol. Interact.

J. Steroid. Mol. Biol.

Marine Environ. Res.

J. Biol. Chem.

Mutation Res.

Ecotox. Environ. Safety

J. Biol. Chem.

Mutation Res.

Mutation Res.

Biochem. Biophys. Res. Commun.

Mutation Res.

Toxicol. Appl. Pharmacol.

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

Proc. Natl. Acad. Sci. USA

Histology and histochemistry of the liver of chickens after chlorinated biphenyls

Arch. Toxicol.

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

Drug Metab. Dispos.

Chemical threat to birds and mammals in the Netherlands

Rev. Environ. Contam. Toxicol.

Liver and kidney DNA adducts formation and chlordane

Toxicol. Lett.

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

Drug Metab. Dispos.

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.