Benzo(a)pyrene-coated onto Fe(2)O(3) particles-induced lung tissue injury: role of free radicals.
Lipid peroxidation (as malondialdehyde; MDA), activities of some antioxidant enzymes (as superoxide dismutase; SOD, glutathione peroxidase; GPx, glutathione reductase; GR), glutathione status, and oxidative DNA damage (as 8-hydroxy-2'-deoxyguanosine; 8-OHdG) were investigated in the lungs of rats exposed to hematite (Fe(2)O(3); 3 mg), benzo(a)pyrene (B(a)P; 3 mg), or B(a)P (3 mg)-coated onto Fe(2)O(3) particles (3 mg). Approximately 2-fold increases in MDA production were seen in animals exposed to Fe(2)O(3), B(a)P, or B(a)P-coated onto Fe(2)O(3) particles (P<0.01). Decreases in SOD activities were observed in rats treated with Fe(2)O(3) (1.66-fold, P<0.01), B(a)P (1.66-fold, P<0.001) or B(a)P-coated onto Fe(2)O(3) particles (1.43-fold, P<0.01). GPx and GR activities could not be detected. No alteration of the glutathione status was observed. Significant increases in the 8-OHdG formation occurred in response to exposure to B(a)P (2.0-fold, P<0.01) or B(a)P-coated onto Fe(2)O(3) particles (23.7-fold, P<0.001). Our results demonstrate also that Fe(2)O(3) generates free radical (FR)-induced lung injury and is not an inert carrier. We established that exposure to B(a)P or B(a)P-coated onto Fe(2)O(3) particles resulted in lipid peroxidation and SOD inactivation, thereby leading to oxidative damages in DNA. The main findings of this work was that B(a)P-coated onto Fe(2)O(3) particles caused higher lung concentrations of 8-OHdG than B(a)P by itself. Hence, our data may explain why exposure to B(a)P-coated onto Fe(2)O(3) particles resulted in a decreased latency and an increased incidence of lung tumors in rodents compared to exposure to B(a)P.
Garçon
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GIP-CERESTE, Laboratoire Universitaire de Médecine du Travail et des Risques Professionnels, Faculté de Médecine-Pôle Recherche, 01, Place de Verdun, 59045 Cedex, Lille, France.
Garry
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Gosset
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Zerimech
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Martin
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A
Hannothiaux
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Shirali
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D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D005290:Ferric Compounds / Q000008:administration & dosage / Q000633:toxicity*; D005609:Free Radicals / Q000378:metabolism* / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008171:Lung Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
D005290:Ferric Compounds; D005609:Free Radicals; C000499:ferric oxide; D001564:Benzo(a)pyrene; D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D003849:Deoxyguanosine; D005978:Glutathione; D019803:Glutathione Disulfide