Effect of Fe(2)O(3) on the capacity of benzo(a)pyrene to induce polycyclic aromatic hydrocarbon-metabolizing enzymes in the respiratory tract of Sprague-Dawley rats.
In this work, the question that needs to be answered was whether concurrent exposure to iron oxides and polycyclic aromatic hydrocarbons (PAHs) could affect the induction of PAH-metabolizing enzymes. Male Sprague-Dawley rats were intratracheally instilled with hematite (Fe(2)O(3); 3mg), benzo(a)pyrene (B(a)P; 3mg), or B(a)P (3mg)-coated onto Fe(2)O(3) particles (3mg). Forty-eight hours later, we investigated mRNA expressions of cytochrome p4501a1 (cyp1a1), microsomal epoxide hydrolase (meh), and glutathione-S-transferase-ya and -yc (gst-ya and gst-yc, respectively), protein concentrations of CYP1A1, and 7-ethoxyresorufin O-deethylase (EROD) activities in lungs. Exposure to B(a)P alone or coated-onto Fe(2)O(3) particles induced cyp1a1 gene transcription (P < 0.01) and increased both the CYP1A1 protein levels (P < 0.01) and the EROD activities (P < 0.001). However, in this work, we focused our attention on the potential of Fe(2)O(3) in B(a)P/Fe(2)O(3) mixtures to affect the capacity of B(a)P to induce PAH-metabolizing enzymes. Exposure to B(a)P-coated onto Fe(2)O(3) particles increased meh mRNA expressions (1.15-fold, P < 0.05), CYP1A1 protein concentrations (1.85-fold, P < 0.05), and EROD activities (1.95-fold, P < 0.01), versus exposure to B(a)P alone. Hence, animal short-term exposure to B(a)P-coated onto Fe(2)O(3) particles favored dramatically the induction of PAH-bioactivating enzymes to the detriment of PAH-inactivating enzymes in lungs. Taken together, these results support the hypothesis that the Fe(2)O(3)-induced increase of the metabolic activation of B(a)P might rely on several properties of Fe(2)O(3), including its capacity to enhance the rate of CYP1A1 hemoprotein elaboration. The influence of Fe(2)O(3) in B(a)P/Fe(2)O(3) mixtures on the ability of B(a)P to induce PAH-metabolizing enzymes will also be one of the fundamental ways that Fe(2)O(3) can affect B(a)P carcinogenicity in lungs.
Garçon
Guillaume
G
Laboratoire de Recherche en Toxicologie Industrielle et Environnementale, Université du Littoral-Côte d'Opale 220, Avenue de l'Université, BP 5526, 59379 Dunkerque Cedex 1, France.
Gosset
Pierre
P
Zerimech
Farid
F
Grave-Descampiaux
Béatrice
B
Shirali
Pirouz
P
D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D004357:Drug Synergism; D004790:Enzyme Induction; D004851:Epoxide Hydrolases / Q000096:biosynthesis; D005290:Ferric Compounds / Q000633:toxicity*; D005982:Glutathione Transferase / Q000096:biosynthesis; D007322:Instillation, Drug; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000393:Air Pollutants; D005290:Ferric Compounds; D012333:RNA, Messenger; C000499:ferric oxide; D001564:Benzo(a)pyrene; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases