Apoptosis and Bax Expression are Increased by Coal Dust in the Polycyclic Aromatic Hydrocarbon–Exposed Lung Mohamed M. Ghanem,1,2 Lori A. Battelli,1,2 Robert R. Mercer,2 James F. Scabilloni,2 Michael L. Kashon,2 Jane Y.C. Ma,2 Joginder Nath,1 and Ann F. Hubbs2 1Genetics and Developmental Biology Program, West Virginia University, Morgantown, West Virginia, USA; 2Health Effect Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia, USA Abstract Background: 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. Methods: 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]. Results: 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. Conclusions: 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. Key words: apoptosis, Bax, caspase, coal dust, CYP1A1, CYP2B1, modifiers, polycyclic aromatic hydrocarbons, pneumoconiosis, xenobiotic metabolism.Environ Health Perspect 114:1367–1373 (2006) . doi:10.1289/ehp.8906 available via http://dx.doi.org/ [Online 18 May 2006] Address correspondence to A. Hubbs, Pathology and Physiology Research Branch, Health Effect Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, 1095 Willowdale Rd., Morgantown, WV 26505 USA. Telephone: (304) 285-6128. Fax: (304) 285-5938. E-mail: Ahubbs@cdc.gov Supplemental Material is available online at http://www.ehponline.org/docs/2006/8906/suppl.pdf We thank P. Willard and L. Millecchia for their assistance in imaging and histotechnology. This manuscript represents a portion of dissertation research submitted to West Virginia University by M.M.G. The Advanced Research Foundation Inc. partially funded a research stipend for M.M.G. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the National Institute for Occupational Safety and Health. The authors declare they have no competing financial interests. Received 7 December 2005 ; accepted 18 May 2006. The full version of this article is available for free in HTML or PDF formats. |