Eberly College of Arts and Sciences
Miners inhaling respirable coal dust (CD) frequently develop coal workers’ pneumoconiosis, a dust-associated pneumoconiosis characterized by lung inflammation and variable fibrosis. Many coal miners are also exposed to polycyclic aromatic hydrocarbon (PAH) components of diesel engine exhaust and cigarette smoke, which may contribute to lung disease in these workers. Recently, apoptosis was reported to play a critical role in the development of another pneumoconiosis of miners, silicosis. In addition, CD was reported to suppress cytochrome P450 1A1 (CYP1A1) induction by PAHs.
We investigated the hypothesis that apoptosis plays a critical role in lung injury and down-regulation of CYP1A1 induction in mixed exposures to CD and PAHs. We exposed rats intratracheally to 0.0, 2.5, 10.0, 20.0, or 40.0 mg/rat CD and, 11 days later, to intraperitoneal β-naphthoflavone (BNF), a PAH. In another group of rats exposed to CD and BNF, caspase activity was inhibited by injection of the pan-caspase inhibitor Q-VD-OPH [quinoline-Val-Asp (OMe)-CH2-OPH].
In rats exposed to BNF, CD exposure increased alveolar expression of the proapoptotic mediator Bax but decreased CYP1A1 induction relative to BNF exposure alone. Pan-caspase inhibition decreased CD-associated Bax expression and apoptosis but did not restore CYP1A1 activity. Further, CD-induced lung inflammation and alveolar epithelial cell hypertrophy and hyperplasia were not suppressed by caspase inhibition.
Combined BNF and CD exposure increased Bax expression and apoptosis in the lung, but Bax and apoptosis were not the major determinants of early lung injury in this model.
Digital Commons Citation
Ghanem, Mohamed M.; Battelli, Lori A.; Mercer, Robert R.; Scabilloni, James F.; Kashon, Michael L.; Ma, Jane Y C; Nath, Joginder; and Hubbs, Ann F., "Apoptosis and Bax Expression are Increased by Coal Dust in the Polycyclic Aromatic Hydrocarbon-Exposed Lung" (2007). Faculty & Staff Scholarship. 2878.
Ghanem, M. M., Battelli, L. A., Mercer, R. R., Scabilloni, J. F., Kashon, M. L., Ma, J. Y. C., Nath, J., & Hubbs, A. F. (2006). Apoptosis and Bax Expression are Increased by Coal Dust in the Polycyclic Aromatic Hydrocarbon-Exposed Lung. Environmental Health Perspectives, 114(9), 1367–1373. https://doi.org/10.1289/ehp.8906