This Article Full Text Full Text (PDF) All Versions of this Article: 2002-0269OCv1 29/2/180    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Upadhyay, D. Articles by Kamp, D. W. Search for Related Content PubMed PubMed Citation Articles by Upadhyay, D. Articles by Kamp, D. W.

Particulate Matter Induces Alveolar Epithelial Cell DNA Damage and Apoptosis

Role of Free Radicals and the Mitochondria

Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Veterans Administration Chicago Health Care System: Lakeside Division, and Department of Medicine, Chicago, Illinois; and National Health and Environmental Effects Research Laboratory, EPA, Research Triangle Park, North Carolina

Address correspondence to: David Kamp, Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, 303 East Chicago Ave., Tarry Bldg., 14-707, Chicago, IL 60611. E-mail: d-kamp{at}northwestern.edu

Airborne particulate matter (PM) increases morbidity and mortality resulting from cardiopulmonary diseases including cancer. We hypothesized that PM is genotoxic to alveolar epithelial cells (AEC) by causing DNA damage and apoptosis. PM caused dose-dependent AEC DNA strand break formation, reductions in mitochondrial membrane potential (_m), caspase 9 activation, and apoptosis. An iron chelator and a free radical scavenger prevented these effects. Finally, overexpression of Bcl-xl, a mitochondrial anti-apoptotic protein, blocked PM-induced _m and DNA fragmentation. We conclude that PM causes AEC DNA damage and apoptosis by mechanisms that involve the mitochondria-regulated death pathway and the generation of iron-derived free radicals.

Abbreviations: alveolar epithelial cells, AEC • deferoxamine, DF • DNA strand break, DNA-SB • double-stranded DNA, ds-DNA • enzyme-linked immunosorbent assay, ELISA • trifluoromethoxyphenlhydrazone, FCCP • particulate matter, PM • Change in mitochondrial membrane potential, _m • sodium benzoate, NaB • phytic acid, PA • particulate matter, PM • reactive oxygen species, ROS • titanium dioxide, TiO₂ • tetremethylrhod-amine ethyl ester, TMRE • terminal deoxynucleotidyl transferase-mediated deoxyuridine-5'-triphosphate-biotin nick end labeling, TUNEL

This article has been cited by other articles:

				S. Soberanes, V. Panduri, G. M. Mutlu, A. Ghio, G. R. S. Bundinger, and D. W. Kamp p53 Mediates Particulate Matter-induced Alveolar Epithelial Cell Mitochondria-regulated Apoptosis Am. J. Respir. Crit. Care Med., December 1, 2006; 174(11): 1229 - 1238. [Abstract] [Full Text] [PDF]

				G. M. Mutlu, C. Snyder, A. Bellmeyer, H. Wang, K. Hawkins, S. Soberanes, L. C. Welch, A. J. Ghio, N. S. Chandel, D. Kamp, et al. Airborne Particulate Matter Inhibits Alveolar Fluid Reabsorption in Mice via Oxidant Generation Am. J. Respir. Cell Mol. Biol., June 1, 2006; 34(6): 670 - 676. [Abstract] [Full Text] [PDF]

				J. W. Anseth, A. J. Goffin, G. G. Fuller, A. J. Ghio, P. N. Kao, and D. Upadhyay Lung Surfactant Gelation Induced by Epithelial Cells Exposed to Air Pollution or Oxidative Stress Am. J. Respir. Cell Mol. Biol., August 1, 2005; 33(2): 161 - 168. [Abstract] [Full Text] [PDF]