Comparison of the biological activity between ultrafine and fine titanium dioxide particles in RAW 264.7 cells associated with oxidative stress

Ultrafine or fine titanium dioxide (TiO2) particles are widely used in the production of white pigments, for sunscreens, and in cleanup techniques. However, currently knowledge is deficient concerning cellular responses to these particles. The study evaluated and compared the biological activity of ultrafine and fine TiO2 particles in RAW 264.7 macrophages according to an oxidative stress paradigm. In vitro exposure of macrophages to ultrafine or fine TiO2 in the range of 0.5-200 μg/ml did not significantly alter cell viability. However, ultrafine TiO2 enhanced intracellular generation of reactive oxygen species (ROS) to a greater extent than fine TiO2 at each exposure concentration. Ultrafine TiO2 induced ERK1/2 activation in a concentration-dependent manner, while the fine TiO2-induced changes were minimal. Phosphorylation of ERK1/2 occurred following 10 min exposure to higher concentrations of ultrafine TiO2 (>25 μg/ml). Similarly, ultrafine TiO2 exposure significantly enhanced tumor necrosis factor (TNF)-α and macrophage inflammatory protein (MIP)-2 secretion in a concentration-dependent manner, and its potency was higher than fine TiO2. These findings suggest that when exposure concentration is based upon equivalent mass, ultrafine TiO2 exerts greater biological activity as measured by ROS generation, ERK 1/2 activation, and proinflammatory mediator secretion in RAW 264.7 macrophages than fine TiO2.