Food-Grade TiO₂ Particles Generate Intracellular Superoxide and Alter Epigenetic Modifiers in Human Lung Cells

Titanium dioxide (TiO₂) particles are a common ingredient in food, providing the bright white color for many candies, gums, and frostings. While ingestion of these materials has been examined previously, few studies have examined the effect of these particles on lung cells. Inhalation is an important exposure pathway for workers processing these foods and, more recently, home users who purchase these particles directly. We examine the response of lung cells to food-grade TiO₂ particles using a combination of fluorescence microscopy and RT-PCR. These experiments show that TiO₂ particles generate intracellular reactive oxygen species, specifically superoxide, and alter expression of two epigenetic modifiers, histone deacetylase 9 (HDAC9) and HDAC10. We use a protein corona formed from superoxide dismutase (SOD), an enzyme that scavenges superoxide, to probe the relationship between TiO₂ particles and superoxide generation. These experiments show that low, non-cytotoxic, concentrations of food-grade TiO₂ particles lead to cellular responses, including altering two enzymes responsible for epigenetic modifications. This production of superoxide and change in epigenetic modifiers could affect human health following inhalation. We expect this research will motivate future in vivo experiments examining the pulmonary response to food-grade TiO₂ particles.