Multigenerational mitochondrial alterations in pneumocytes exposed to oil fly ash metals

Abstract

Oil fly ash (OFA), containing high amounts of transition metals, is among the most reactive airborne particulate matter emissions, which have been associated with several diseases, such as chronic obstructive pulmonary diseases (COPD), lung cancer, and cardiovascular diseases. The aim of the present study was to evaluate mitochondrial alterations in OFA-exposed cultured pneumocytes and in their progeny. Alveolar epithelial cells (A549 line) were exposed either to an OFA water solution, containing 68.8 μM vanadium (V), 110.4 μM iron (Fe), and 18.0 μM nickel (Ni), or to the individual metal solutions. Structural and functional mitochondrial parameters were determined in exposed cultures and in 3 consecutive subcultures. OFA, V and Fe solutions caused a time-dependent loss of mitochondrial enzymatic activity, glutathione depletion, generation of lipid hydroperoxides, hydrogen peroxide and other reactive oxygen species, especially in G(0)-G(1) phase cells, accompanied by a decrease in mitochondrial mass and transmembrane potential. Mitochondrial alterations were partly transmissible to daughter cells for up to 3 generations. Fe and especially V were responsible for the observed mitochondrial alterations in pneumocytes exposed to OFA. Spread of mitochondrial dysfunctions to daughter cells is expected to amplify oxidative stress in the respiratory epithelium and to play an important role in the pathogenesis of respiratory diseases.