Influence of iron (56Fe2O3 or 54Fe2O3) in the upregulation of cytochrome P4501A1 by benzo[a]pyrene in the respiratory tract of Sprague-Dawley rats

Authors

  • Guillaume Garçon,

    1. Laboratoire de Recherche en Toxicologie Industrielle et Environnementale, Maison de la Recherche en Environnement Industriel de Dunkerque 2, 189A Avenue Maurice Schumann, 59140 Dunkerque, France
    Search for more papers by this author
  • Pierre Gosset,

    1. Laboratoire d'Anatomie et de Cytologie Pathologique du Groupement Hospitalier de l'Institut Catholique de Lille, Faculté Libre de Médecine, 56, rue du Port, 59046 Lille Cedex, France
    Search for more papers by this author
  • Benoît Maunit,

    1. Laboratoire de Spectrométrie de Masse et de Chimie Laser, Université de Metz, 01, boulevard Arago, 57078 Metz Cedex 3, France
    Search for more papers by this author
  • Farid Zerimech,

    1. Laboratoire de Biochimie et de Biologie Moleculaire, Hôpital Huriez, 01, Place de Verdun, 59045 Lille Cedex, France
    Search for more papers by this author
  • Colette Creusy,

    1. Laboratoire d'Anatomie et de Cytologie Pathologique du Groupement Hospitalier de l'Institut Catholique de Lille, Faculté Libre de Médecine, 56, rue du Port, 59046 Lille Cedex, France
    Search for more papers by this author
  • Jean-François Muller,

    1. Laboratoire de Spectrométrie de Masse et de Chimie Laser, Université de Metz, 01, boulevard Arago, 57078 Metz Cedex 3, France
    Search for more papers by this author
  • Pirouz Shirali

    Corresponding author
    1. Laboratoire de Recherche en Toxicologie Industrielle et Environnementale, Maison de la Recherche en Environnement Industriel de Dunkerque 2, 189A Avenue Maurice Schumann, 59140 Dunkerque, France
    • Laboratoire de Recherche en Toxicologie Industrielle et Environnementale, Maison de la Recherche en Environnement Industriel de Dunkerque 2, 189A Avenue Maurice Schumann, 59140 Dunkerque, France.
    Search for more papers by this author

Abstract

Any influence of iron in polycyclic aromatic hydrocarbon (PAH)/iron oxide mixtures on the capacity of PAHs to induce metabolizing enzymes will be one of the ways that iron oxides can affect PAH carcinogenicity. Because cytochromes P450 (CYPs) are haemoproteins, it will be of interest to investigate the possible involvement of Fe2O3 in benzo[a]pyrene (BaP)/Fe2O3 mixtures on the induction of CYP1A1 enzymes in the lung. Male Sprague-Dawley rats were instilled intratracheally with haematite (56Fe2O3 or 54Fe2O3, 3 mg), BaP (3 mg) or BaP (3 mg) coated onto haematite (56Fe2O3 or 54Fe2O3) particles (3 mg). Firstly, mRNA expressions of cyp1a1 were studied. Secondly, protein concentrations and catalytic activities (7-ethoxyresorufin O-deethylase: EROD) of CYP1A1 were determined. Thirdly, 54Fe from BaP/54Fe2O3 mixtures in microsomal proteins was studied using time-of-flight laser microprobe mass spectrometry (ToF-LMMS). Statistically significant increases in mRNA expressions, protein concentrations and catalytic activities of CYP1A1 were observed in animals exposed to BaP, to BaP coated onto 56Fe2O3 particles or to BaP coated onto 54Fe2O3 particles versus controls. Both of the BaP/Fe2O3 mixtures induced higher CYP1A1 protein levels and EROD activities than BaP alone. Iron oxide particles per se did not affect mRNA levels of cyp1a1 but only enhanced BaP-mediated increases of CYP1A1 protein levels and activity. The ToF-LMMS spectrum profiles showed that the 54Fe/56Fe ratio in the microsomes of BaP coated onto 54Fe2O3 particle-instilled animals was 1.3 instead of the theoretical ratio (i.e. 0.063) observed in BaP coated onto 56Fe2O3 particle-instilled animals. Taken together, these novel data support the hypothesis that the Fe2O3-induced increases of the metabolic activation of BaP might rely on the property of Fe2O3 particles to enhance the BaP-induced translation rate of the cyp1a1 gene into functional haemoproteins. Copyright © 2004 John Wiley & Sons, Ltd.

Ancillary