title: Particulate matter induces alveolar epithelial cell DNA damage and apoptosis: role of free radicals and the mitochondria.
abstract: 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 (Delta psi 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 Delta psi 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.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, and Department of Medicine, Veterans Administration Chicago Healthcare System, Lakeside Division, Chicago, IL 60611, USA.
authors.forename: Daya
authors.initials: D
authors.lastname: Upadhyay
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Panduri
authors.forename: Andrew
authors.initials: A
authors.lastname: Ghio
authors.forename: David W
authors.initials: DW
authors.lastname: Kamp
mesh_terms: D017209:Apoptosis; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D007501:Iron / Q000494:pharmacology; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species; D013696:Temperature; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein
chemical_list: C494811:BCL2L1 protein, human; D002614:Chelating Agents; D005609:Free Radicals; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051020:bcl-X Protein; D007501:Iron; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases