Research

Lung inflammation and genotoxicity following pulmonary exposure to nanoparticles in ApoE^-/- mice

Nicklas Raun Jacobsen¹ , Peter Møller² , Keld Alstrup Jensen¹ , Ulla Vogel^1,3,4 , Ole Ladefoged³ , Steffen Loft² and Håkan Wallin¹

¹  National Research Centre for the Working Environment, Lersø Parkallé 105, DK-2100 Copenhagen Ø, Denmark

²  Department of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark

³  Department for Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, DK-2860 Søborg, Denmark

⁴  Institute for Science, Systems and Models, University of Roskilde, DK-4000 Roskilde, Denmark

author email corresponding author email

Particle and Fibre Toxicology 2009, 6:2doi:10.1186/1743-8977-6-2

Published:	12 January 2009

Abstract

Background

The toxic and inflammatory potential of 5 different types of nanoparticles were studied in a sensitive model for pulmonary effects in apolipoprotein E knockout mice (ApoE^-/-). We studied the effects instillation or inhalation Printex 90 of carbon black (CB) and compared CB instillation in ApoE-/- and C57 mice. Three and 24 h after pulmonary exposure, inflammation was assessed by mRNA levels of cytokines in lung tissue, cell composition, genotoxicity, protein and lactate dehydrogenase activity in broncho-alveolar lavage (BAL) fluid.

Results

Firstly, we found that intratracheal instillation of CB caused far more pulmonary toxicity in ApoE^-/- mice than in C57 mice. Secondly, we showed that instillation of CB was more toxic than inhalation of a presumed similar dose with respect to inflammation in the lungs of ApoE^-/- mice. Thirdly, we compared effects of instillation in ApoE^-/- mice of three carbonaceous particles; CB, fullerenes C₆₀ (C₆₀) and single walled carbon nanotubes (SWCNT) as well as gold particles and quantum dots (QDs). Characterization of the instillation media revealed that all particles were delivered as agglomerates and aggregates. Significant increases in Il-6, Mip-2 and Mcp-1 mRNA were detected in lung tissue, 3 h and 24 h following instillation of SWCNT, CB and QDs. DNA damage in BAL cells, the fraction of neutrophils in BAL cells and protein in BAL fluid increased statistically significantly. Gold and C₆₀ particles caused much weaker inflammatory responses.

Conclusion

Our data suggest that ApoE^-/- model is sensitive for evaluating particle induced inflammation. Overall QDs had greatest effects followed by CB and SWCNT with C₆₀ and gold being least inflammatory and DNA-damaging. However the gold was used at a much lower mass dose than the other particles. The strong effects of QDs were likely due to Cd release. The surface area of the instilled dose correlated well the inflammatory response for low toxicity particles.