Benzo(a)pyrene-coated onto Fe sub(2)O sub(3) particles-induced apoptotic events in the lungs of Sprague-Dawley rats

• Published in: Toxicology letters Vol. 143; no. 2; pp. 223 - 232
• Main Authors: Gosset, P, Garcon, G, Casset, A, Fleurisse, L, Hannothiaux, M H, Creusy, C, Shirali, P
• Format: Journal Article
• Language: English
• Published: 01-07-2003
• ISSN: 0378-4274
• DOI: 10.1016/S0378-4274(03)00153-X

Because benzo(a)pyrene (B(a)P)-coated onto hematite (Fe sub(2)O sub(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 sub(2)O sub(3) (3 mg), B(a)P (3 mg) or B(a)P (3 mg)-coated onto Fe sub(2)O sub(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 sub(2)O sub(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 sub(2)O sub(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 sub(2)O sub(3) (1.73-fold, P<0.01) or B(a)P-coated onto Fe sub(2)O sub(3) particles (1.53-fold, P<0.01) was observed. Taken together, the present results support the underlying hypothesis that the influence of Fe sub(2)O sub(3) in B(a)P/Fe sub(2)O sub(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 sub(2)O sub(3) can affect B(a)P toxicity in lungs.