DIFFERENCES IN THE EFFECTS OF FIBROUS AND PARTICULATE TITANIUM DIOXIDE ON ALVEOLAR MACROPHAGES OF FISCHER 344 RATS

Abstract

Alveolar macrophages are considered to play a major role in the pathophysiology of lung diseases caused by exposure to various kinds of pathogens and particles. In this study, the cytotoxic effect of different shapes of titanium dioxide (TiO 2 ) was evaluated on macrophages using a unique magnetometry method and was compared with conventional methods of lactate dehydrogenase (LDH) release, apoptosis measurement, and morphological observations. Alveolar macrophages obtained from Fischer rats (F344) by bronchoalveolar lavage were incubated in vitro for 18 h with Fe 3 O 4 as a magnetometric indicator and fibrous and particulate forms of TiO 2 as test materials. In the control and particulate exposed group, rapid attenuation of the residual magnetic field, so-called "relaxation," was observed immediately after cessation of the external magnetic field. In comparison, a delay of relaxation was observed in alveolar macrophages exposed to fibrous TiO 2 . LDH released into serum-free medium induced by exposure to TiO 2 increased significantly in a concentration-dependent manner in macrophages exposed to fibrous TiO 2 , while negligible LDH release was observed in macrophages exposed to particulate TiO 2 . The DNA ladder detection method and morphological examination detected no apoptosis in macrophages exposed to 60 µg/ml of fibrous or particulate TiO 2 . Electron microscopic examination revealed vacuolar changes and cell surface damage in macrophages exposed to fibrous TiO 2 , but no significant changes in macrophages exposed to particulate TiO 2 . The results of magnetometry, LDH release, and electron microscopy suggest that cytotoxicity of TiO 2 depends on the shape of the material.