Genotoxicity of inhaled nanosized TiO2 in mice

Nanosafety Research Center, Finnish Institute of Occupational Health, FI-00250 Helsinki, Finland.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis (Impact Factor: 4.44). 11/2011; 745(1-2):58-64. DOI: 10.1016/j.mrgentox.2011.10.011
Source: PubMed

ABSTRACT In vitro studies have suggested that nanosized titanium dioxide (TiO(2)) is genotoxic. The significance of these findings with respect to in vivo effects is unclear, as few in vivo studies on TiO(2) genotoxicity exist. Recently, nanosized TiO(2) administered in drinking water was reported to increase, e.g., micronuclei (MN) in peripheral blood polychromatic erythrocytes (PCEs) and DNA damage in leukocytes. Induction of micronuclei in mouse PCEs was earlier also described for pigment-grade TiO(2) administered intraperitoneally. The apparent systemic genotoxic effects have been suggested to reflect secondary genotoxicity of TiO(2) due to inflammation. However, a recent study suggested that induction of DNA damage in mouse bronchoalveolar lavage (BAL) cells after intratracheal instillation of nanosized or fine TiO(2) is independent of inflammation. We examined here, if inhalation of freshly generated nanosized TiO(2) (74% anatase, 26% brookite; 5 days, 4 h/day) at 0.8, 7.2, and (the highest concentration allowing stable aerosol production) 28.5 mg/m(3) could induce genotoxic effects in C57BL/6J mice locally in the lungs or systematically in peripheral PCEs. DNA damage was assessed by the comet assay in lung epithelial alveolar type II and Clara cells sampled immediately following the exposure. MN were analyzed by acridine orange staining in blood PCEs collected 48 h after the last exposure. A dose-dependent deposition of Ti in lung tissue was seen. Although the highest exposure level produced a clear increase in neutrophils in BAL fluid, indicating an inflammatory effect, no significant effect on the level of DNA damage in lung epithelial cells or micronuclei in PCEs was observed, suggesting no genotoxic effects by the 5-day inhalation exposure to nanosized TiO(2) anatase. Our inhalation exposure resulted in much lower systemic TiO(2) doses than the previous oral and intraperitoneal treatments, and lung epithelial cells probably received considerably less TiO(2) than BAL cells in the earlier intratracheal study.

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Available from: Antti Joonas Koivisto, Jan 12, 2014
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    • "Alltogether 46 studies investigating the in vivo genotoxicity of nanomaterials were identified by literature search. 19 of these studies were negative (Lindberg et al., 2012; Landsiedel et al., 2010; Saber et al., 2011; Naya et al., 2012; Rehn et al., 2003; Boisen et al., 2012; Ema et al., 2012; Wessels et al., 2011; Wu et al., 2010; Estevanato et al., 2011; Kim et al., 2011; Kim et al., 2008; Schulz et al., 2012; Sayes et al., 2010; Dandekar et al., 2010; Shinohara et al., 2009; Sadiq et al., 2012; Tavares et al., 2012; Li et al., 2012b). Note that most of these studies do not indicate a lack of evidence for genotoxicity as the doses tested were low and/or it was not shown that the material reached the tissue investigated for genotoxicity in sufficient amounts. "
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