Genotoxicity of inhaled nanosized TiO2 in mice
| Autor: | Harri Alenius, Ghita C.-M. Falck, Carlos Moreno, Antti Joonas Koivisto, Satu Suhonen, Kai Savolainen, Hilkka Järventaus, Yrjö Peltonen, Timo Tuomi, Hannu Norppa, Hanna K. Lindberg, Heli Nykäsenoja, Elina M. Rossi, Julia Catalán |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Health Toxicology and Mutagenesis medicine.disease_cause Mice chemistry.chemical_compound Administration Inhalation Genetics medicine Animals Lung Inflammation Titanium Inhalation exposure Micronucleus Tests medicine.diagnostic_test Inhalation Acridine orange technology industry and agriculture Molecular biology Mice Inbred C57BL Comet assay Bronchoalveolar lavage chemistry Immunology Micronucleus test Nanoparticles Comet Assay Micronucleus Genotoxicity DNA Damage Mutagens |
| Zdroj: | Mutation Research/Genetic Toxicology and Environmental Mutagenesis. 745:58-64 |
| ISSN: | 1383-5718 |
| DOI: | 10.1016/j.mrgentox.2011.10.011 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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