Genotoxicity of inhaled nanosized TiO₂ in mice

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• 作者：Hanna K. Lindberg^a ; ^b ; Ghita C.-M. Falck^a ; ^b ; Julia Catalá ; n^a ; ^b ; ^c ; Antti J. Koivisto^a ; ^b ; Satu Suhonen^a ; ^b ; Hilkka Jä ; rventaus^a ; ^b ; Elina M. Rossi^a ; ^d ; Heli Nykä ; senoja^a ; ^d ; Yrjö ; Peltonen^a ; ^b ; Carlos Moreno^c ; Harri Alenius^a ; ^d ; Timo Tuomi^e ; Kai M. Savolainen^a ; Hannu Norppa^a ; ^b ; ^{hannu.norppa@ttl.fi}
• 关键词：Anatase ; Blood erythrocyte ; Comet assay ; Genotoxicity ; Lung ; Micronucleus
• 刊名：Mutation Research/Genetic Toxicology and Environmental Mutagenesis
• 出版年：2012
• 期刊代码：31_13835718
• 类别：pha
• 出版时间：14 June, 2012
• 卷：745
• 期：1-2
• 页码：58-64
• 文件大小：295 K

摘要

In vitro studies have suggested that nanosized titanium dioxide (TiO₂) is genotoxic. The significance of these findings with respect to in vivo effects is unclear, as few in vivo studies on TiO₂ genotoxicity exist. Recently, nanosized TiO₂ 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 TiO₂ administered intraperitoneally. The apparent systemic genotoxic effects have been suggested to reflect secondary genotoxicity of TiO₂ 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 TiO₂ is independent of inflammation. We examined here, if inhalation of freshly generated nanosized TiO₂ (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/m³ 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 TiO₂ anatase. Our inhalation exposure resulted in much lower systemic TiO₂ doses than the previous oral and intraperitoneal treatments, and lung epithelial cells probably received considerably less TiO₂ than BAL cells in the earlier intratracheal study.