Macrophage toxicity in response to particles collected from indium-tin oxide production.
Badding MA; Fix NR; Dunnick KM; Cummings KJ; Castranova V; Leonard SS
Toxicologist 2013 Mar; 132(1):427
Occupational exposure to indium compounds has recently been associated with lung disease among workers in the indium-tin oxide (ITO) industry. Previous studies have suggested that autoantibodies and reactive oxygen species (ROS) may play a role in the development of pulmonary lesions following indium compound exposures. However, the molecular mechanisms behind indium compounds' toxicity remain largely unknown. Thus, we aim to uncover how compounds encountered in the ITO production process affect cultured macrophages and ultimately, contribute to the pathogenesis of indium lung disease. The indium compounds used in this study were collected from different process stages at an ITO production facility. Darkfield microscopy has revealed that various indium compounds interact with the cells as early as 5 minutes post-exposure, suggesting that cellular reactions to the ITO compounds may be occurring very rapidly. Indeed, using electron spin resonance (ESR) to measure ROS generation, we found that various collected indium compounds produce free radicals in the presence and absence of RAW 264.7 mouse macrophages within 5 minutes. We also hypothesize that indium compound particle uptake by macrophages leads to subsequent cellular damage, which could be contributing to lung pathology. Therefore, various imaging techniques are being used to observe particle association with and uptake by macrophages over a time course. Current studies are underway to evaluate the effects of the collected indium compounds on intracellular ROS production, lipid peroxidation, DNA damage, and cell proliferation over the same time course. These findings will provide a foundation for the molecular basis behind an emerging occupational health issue and assist in the prevention indium lung disease.
Toxicology; Laboratory-animals; Exposure-levels; Pulmonary-function; Pulmonary-system-disorders; Lung-function; Dose-response; Lung-disorders; Lung-irritants; Respiratory-system-disorders; Tin-oxides; Oxides; Antibody-response; Pathogenesis; Cell-alteration; Cell-cultures; Cellular-function; Cellular-reactions; Free-radical-generation; Free-radicals; Cellular-uptake; Lung-cells; Lipid-peroxidation; DNA-damage
The Toxicologist. Society of Toxicology 52nd Annual Meeting and ToxExpo, March 10-14, 2013, San Antonio, Texas