Abstract 3606: Effect of anatase type nanosized titanium dioxide particles on the rat lung and cultured macrophage.
Authors: Numano Takamasa , Xu Jiegou , Futakuchi Mitsuru , Fukamachi Katsumi , Furukawa Fumio , Suzui Masumi , Tsuda Hiroyuki 
Published: August 2014

Abstract
Nanosized titanium dioxide is mainly categorized into anatase type (anatase type nTiO2) and rutile type (rutile type nTiO2), and widely used in industry, commercial products and biosystems. Previous our report indicated that rutile type nTiO2 caused the growth of A549 human lung carcinoma cells, induction of macrophage, an increase of 8-hydroxydeoxyguanosine (8-OHdG) and overexpression of Macrophage inflammatory protein 1α(MIP1α). Furthermore, under ultraviolet irradiation, anatase type nTiO2 is 100 times more toxic than rutile type nTiO2 in vitro. In the present study, we compared the pulmonary toxic effects induced by anatase type nTiO2 and rutile type nTiO2. Female SD rats were treated with anatase type nTiO2 or rutile type nTiO2 by intrapulmonary spraying for 8 times over a two week period. Obvious lung inflammation foci were not observed in the rats treated with anatase type nTiO2 or rutile type nTiO2. Infiltration of alveolar macrophages was observed throughout the lung tissues and anatase type nTiO2 or rutile type nTiO2 particles were exclusively phagocytosed by alveolar macrophages. Treatment with both anatase type nTiO2 and rutile type nTiO2 also increased number of alveolar macrophage and the production of 8-OHdG in the lung tissue, with a littler higher in the rutile type nTiO2 treated group than in the anatase type nTiO2 treated group. Importantly, expression of MIP1α in the lung tissue treated with anatase type nTiO2 and rutile type nTiO2 as either mRNA level and protein level was significantly up-regulated compared with that of the control group, with significantly lower in the anatase type nTiO2 treated group than in the rutile type nTiO2 treated group. Similarly, anatase type nTiO2 induced significantly lower mRNA expression of MIP1α in primary alveolar macrophages (PAM) and protein level of MIP1α in the supernatants of PAM cell culture than rutile type nTiO2. Additionally, supernatants of PAM cell culture treated with anatase type nTiO2 had less effect on the growth of A549 cell than those treated with rutile type nTiO2. Conclusively, treatment with both anatase type nTiO2 and rutile type nTiO2 did not cause notable lung inflammation. Analysis of alveolar macrophage induction, production of 8-OHdG in the lung tissue, and MIP1α expression both in vivo in the lung and in vitro in PAM indicated that anatase type nTiO2 was less effective than rutile type nTiO2, partly due to low photocatalytic effect in the lung tissue.
Citation Format: Takamasa Numano, Jiegou Xu, Mitsuru Futakuchi, Katsumi Fukamachi, Fumio Furukawa, Masumi Suzui, Hiroyuki Tsuda. Effect of anatase type nanosized titanium dioxide particles on the rat lung and cultured macrophage. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3606. doi:10.1158/1538-7445.AM2013-3606