Acute phase response and inflammation following pulmonary exposure to low doses of zinc oxide nanoparticles in mice

Inhalation of nanosized zinc oxide (ZnO) induces metal fume fever and systemic acute phase
response in humans. Acute phase response activation is a cardiovascular risk factor; we investigated whether pulmonary exposure of mice can be used to assess ZnO-induced acute phase
response as well as inflammation and genotoxicity. Uncoated (NM-110) and triethoxycaprylylsilane-coated (NM-111) ZnO nanoparticles were intratracheally instilled once at 0.2, 0.7 or 2 mg/
mouse (11, 33 and 100 mg/kg body weight). Serum amyloid A3 mRNA level in lung tissue, bronchoalveolar lavage (BAL) fluid cellularity, and levels of DNA strand breaks in BAL fluid cells, lung
and liver tissue were assessed 1, 3 and 28 days post-exposure. Global transcription patterns
were assessed in lung tissue using microarrays. The acute-phase response serum amyloid A3
mRNA levels were increased on day 1; for uncoated ZnO nanoparticles at the highest dose and
for coated ZnO nanoparticles at medium and highest dose. Neutrophils were increased in BAL
fluid only after exposure to coated ZnO nanoparticles. Genotoxicity was observed only in single
dose groups, with no dose-response relationship. Most changes in global transcriptional
response were observed after exposure to uncoated ZnO nanoparticles and involved cell cycle
G2 to M phase DNA damage checkpoint regulation. [...]