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Influence of iron ( 56 Fe 2 O 3 or 54 Fe 2 O 3 ) in the upregulation of cytochrome P4501A1 by benzo[ a ]pyrene in the respiratory tract of Sprague‐Dawley rats
Author(s) -
Garçon Guillaume,
Gosset Pierre,
Maunit Benoît,
Zerimech Farid,
Creusy Colette,
Muller JeanFrançois,
Shirali Pirouz
Publication year - 2004
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.979
Subject(s) - chemistry , pyrene , benzo(a)pyrene , carcinogen , cytochrome p450 , microsome , enzyme , iron oxide , hydrocarbon , catalysis , nuclear chemistry , messenger rna , cytochrome , biochemistry , organic chemistry , gene
Any inuence 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 Fe 2 O 3 in benzo[ a ]pyrene (BaP)/Fe 2 O 3 mixtures on the induction of CYP1A1 enzymes in the lung. Male Sprague‐Dawley rats were instilled intratracheally with haematite ( 56 Fe 2 O 3 or 54 Fe 2 O 3 , 3 mg), BaP (3 mg) or BaP (3 mg) coated onto haematite ( 56 Fe 2 O 3 or 54 Fe 2 O 3 ) particles (3 mg). Firstly, mRNA expressions of cyp1a1 were studied. Secondly, protein concentrations and catalytic activities (7‐ethoxyresorun O ‐deethylase: EROD) of CYP1A1 were determined. Thirdly, 54 Fe from BaP/ 54 Fe 2 O 3 mixtures in microsomal proteins was studied using time‐of‐ight laser microprobe mass spectrometry (ToF‐LMMS). Statistically signicant increases in mRNA expressions, protein concentrations and catalytic activities of CYP1A1 were observed in animals exposed to BaP, to BaP coated onto 56 Fe 2 O 3 particles or to BaP coated onto 54 Fe 2 O 3 particles versus controls. Both of the BaP/Fe 2 O 3 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 proles showed that the 54 Fe/ 56 Fe ratio in the microsomes of BaP coated onto 54 Fe 2 O 3 particle‐instilled animals was 1.3 instead of the theoretical ratio (i.e. 0.063) observed in BaP coated onto 56 Fe 2 O 3 particle‐instilled animals. Taken together, these novel data support the hypothesis that the Fe 2 O 3 ‐induced increases of the metabolic activation of BaP might rely on the property of Fe 2 O 3 particles to enhance the BaP‐induced translation rate of the cyp1a1 gene into functional haemoproteins. Copyright © 2004 John Wiley & Sons, Ltd.