Benzo(a)pyrene-coated onto Fe2O3 particles-induced apoptotic events in the lungs of Sprague-Dawley rats.
Because benzo(a)pyrene (B(a)P)-coated onto hematite (Fe(2)O(3)) particle-induced adverse effects might alter cell homeostasis in lungs, we investigated the induction of some apoptotic events by such a concurrent exposure on this relevant organ target. Sprague-Dawley rats were intratracheally instilled with Fe(2)O(3) (3 mg), B(a)P (3 mg) or B(a)P (3 mg)-coated onto Fe(2)O(3) particles (3 mg). Forty-eight hours later, both the tumor necrosis factor-receptor and the mitochondrial pathways were studied. We found that exposure to B(a)P (1.13-fold, P<0.05) or to B(a)P-coated onto Fe(2)O(3) particles (1.15-fold, P<0.05) increased caspase 3 activity. However, only the concurrent exposure activated both the caspases 8 (1.21-fold, P<0.05) and 9 (1.27-fold, P<0.05). After exposure to either chemical alone, there was a discrepancy between the findings on tumor necrosis factor-alpha and caspase 8, on one hand, and on cytochrome c and caspase 9, on the other hand. Hence, we suggested that the oxidative stress induced by Fe(2)O(3) or B(a)P will continuously lower or deplete caspase activities, thereby reducing or even avoiding the activation of the apoptotic pathways. In addition, transcriptional induction of p53 gene by Fe(2)O(3) (1.73-fold, P<0.01) or B(a)P-coated onto Fe(2)O(3) particles (1.53-fold, P<0.01) was observed. Taken together, the present results support the underlying hypothesis that 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 some of the events firmly involved in the apoptotic pathways will also be one of the ways that Fe(2)O(3) can affect B(a)P toxicity in lungs.
Gosset
Pierre
P
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 Cedex, Lille, France.
Garçon
Guillaume
G
Casset
Anne
A
Fleurisse
Laurence
L
Hannothiaux
Marie Hélène
MH
Creusy
Colette
C
Shirali
Pirouz
P
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D005290:Ferric Compounds; D016158:Genes, p53 / Q000235:genetics; D008168:Lung / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008863:Microspheres; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D003574:Cytochrome c Group; D005290:Ferric Compounds; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C000499:ferric oxide; D001564:Benzo(a)pyrene; D020169:Caspases