Julie A. Bourdon

Exposure to nanoparticles has been associated with inflammation-related progression of atherosclerosis. To examine nanoparticle-induced cardiac effects in more detail, we characterized heart gene expression profiles alongside plasma proteins associated with cardiovascular disease in C57BL/6 mice intratracheally instilled with vehicle or 0.162 mg Printex 90 carbon black nanoparticles (CBNPs). Mice were killed 1, 3, and 28 days after the exposure and expression profiles were derived using DNA microarrays. Cardiac gene expression was unperturbed by CBNP exposure in two independent experiments, despite substantive changes in pulmonary and hepatic gene expression. MicroRNAs were not affected. Plasma levels of cell adhesion molecules (sE-selectin, sICAM-1, sVCAM-1) and total PAI-1 were immediately increased up to day 3, whereas Apo-A1 and Apo-E were marginally decreased on day 1. These data suggest that though adverse cardiovascular effects are likely following CBNP exposure, these effects are unlikely to be mediated by major direct effects on cardiac gene expression.

Background: Widespread occupational exposure to carbon black nanoparticles (CBNPs) raises concerns over their safety. CBNPs are genotoxic in vitro but less is known about their genotoxicity in various organs in vivo. Methods: We investigated inflammatory and acute phase responses, DNA strand breaks (SB) and oxidatively damaged DNA in C57BL/6 mice 1, 3 and 28 days after a single instillation of 0.018, 0.054 or 0.162 mg Printex 90 CBNPs, alongside sham controls. Bronchoalveolar lavage (BAL) fluid was analyzed for cellular composition. SB in BAL cells, whole lung and liver were assessed using the alkaline comet assay. Formamidopyrimidine DNA glycosylase (FPG) sensitive sites were assessed as an indicator of oxidatively damaged DNA. Pulmonary and hepatic acute phase response was evaluated by Saa3 mRNA real-time quantitative PCR. Results: Inflammation was strongest 1 and 3 days post-exposure, and remained elevated for the two highest doses (i.e., 0.054 and 0.162 mg) 28 days post-exposure (P < 0.001). SB were detected in lung at all doses on post-exposure day 1 (P < 0.001) and remained elevated at the two highest doses until day 28 (P < 0.05). BAL cell DNA SB were elevated relative to controls at least at the highest dose on all post-exposure days (P < 0.05). The level of FPG sensitive sites in lung was increased throughout with significant increases occurring on post-exposure days 1 and 3, in comparison to controls (P < 0.001-0.05). SB in liver were detected on post-exposure days 1 (P < 0.001) and 28 (P < 0.001). Polymorphonuclear (PMN) cell counts in BAL correlated strongly with FPG sensitive sites in lung (r = 0.88, P < 0.001), whereas no such correlation was observed with SB (r = 0.52, P = 0.08). CBNP increased the expression of Saa3 mRNA in lung tissue on day 1 (all doses), 3 (all doses) and 28 (0.054 and 0.162 mg), but not in liver. Conclusions: Deposition of CBNPs in lung induces inflammatory and genotoxic effects in mouse lung that persist considerably after the initial exposure. Our results demonstrate that CBNPs may cause genotoxicity both in the primary exposed tissue, lung and BAL cells, and in a secondary tissue, the liver.