Particulate matter induces alveolar epithelial cell DNA damage and apoptosis - Role of free radicals and the mitochondria

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 (Deltapsi(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 DeltaPsi(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.