DNA strand breaks, acute phase response and inflammation following pulmonary exposure by instillation to the diesel exhaust particle NIST1650b in mice.

Abstract

We investigated the inflammatory response, acute phase response and genotoxic effect of diesel exhaust particles (DEPs, NIST1650b) following a single intratracheal instillation. C57BL/6J BomTac mice received 18, 54 or 162 µg/mouse and were killed 1, 3 and 28 days post-exposure. Vehicle controls and the benchmark particle carbon black (CB, Printex 90; 162 µg/mouse) were tested alongside for comparison. The cellular composition and protein concentration were determined in bronchoalveolar lavage (BAL) fluid as markers for an inflammatory response. Pulmonary and systemic genotoxicity was analysed by the alkaline comet assay as DNA strand breaks in BAL cells, lung and liver tissue. The pulmonary acute phase response was analysed by Saa3 mRNA levels by real-time quantitative polymerase chain reaction. Instillation of DEP induced a strong neutrophil influx 1 and 3 days, but not 28 days post-exposure. Saa3 mRNA levels were increased at all time point for the highest dose and 28 days post-exposure for the middle dose. DEP increased levels of DNA strand breaks in lung tissue for all doses 1 day post-exposure and after 28 days for mid- and high-dose groups. Pulmonary exposure to DEP induced transient inflammation but long-lasting pulmonary acute phase response as well as genotoxicity in lung tissue 28 days post-exposure. The observed long-term pulmonary genotoxicity by DEP was less than the previously observed genotoxicity for CB using identical experimental set-up.

• Authors: Zdenka O Kyjovska, Nicklas R Jacobsen, Anne T Saber, Stefan Bengtson, Petra Jackson, Håkan Wallin, Ulla Vogel
• Journal: Mutagenesis (Mutagenesis) Vol. 30 Issue 4 Pg. 499-507 (Jul 2015) ISSN: 1464-3804 [Electronic] England
• PMID: 25771385 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• RNA, Messenger
• Saa3 protein, mouse
• Serum Amyloid A Protein
• Vehicle Emissions

Topics

• Acute-Phase Reaction (etiology, metabolism, pathology)
• Animals
• Bronchoalveolar Lavage Fluid
• Cells, Cultured
• Comet Assay
• DNA Damage
• Female
• Mice
• Mice, Inbred C57BL
• Pneumonia (etiology, metabolism, pathology)
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Serum Amyloid A Protein (genetics, metabolism)
• Vehicle Emissions (toxicity)