Technical University of Denmark, National Food Institute, Lyngby, Denmark.
The National Research Centre for the Working Environment, Lersø Parkallé 105, DK-2100, Copenhagen Ø, Denmark.
Part Fibre Toxicol. 2018 Jan 3;15(1):2. doi: 10.1186/s12989-017-0238-9.
Little is known about the mechanism underlying the genotoxicity observed in the liver following pulmonary exposure to carbon black (CB) nanoparticles (NPs). The genotoxicity could be caused by the presence of translocated particles or by circulating inflammatory mediators released during pulmonary inflammation and acute-phase response. To address this, we evaluated induction of pulmonary inflammation, pulmonary and hepatic acute-phase response and genotoxicity following exposure to titanium dioxide (TiO), cerium oxide (CeO) or CB NPs. Female C57BL/6 mice were exposed by intratracheal instillation, intravenous injection or oral gavage to a single dose of 162 μg NPs/mouse and terminated 1, 28 or 180 days post-exposure alongside vehicle control.
Liver DNA damage assessed by the Comet Assay was observed after intravenous injection and intratracheal instillation of CB NPs but not after exposure to TiO or CeO. Intratracheal exposure to NPs resulted in pulmonary inflammation in terms of increased neutrophils influx for all NPs 1 and 28 days post-exposure. Persistent pulmonary acute phase response was detected for all NPs at all three time points while only a transient induction of hepatic acute phase response was observed. All 3 materials were detected in the liver by enhanced darkfield microscopy up to 180 days post-exposure. In contrast to TiO and CeO NPs, CB NPs generated ROS in an acellular assay.
Our results suggest that the observed hepatic DNA damage following intravenous and intratracheal dosing with CB NPs was caused by the presence of translocated, ROS-generating, particles detected in the liver rather than by the secondary effects of pulmonary inflammation or hepatic acute phase response.
肺部暴露于碳黑（CB）纳米颗粒（NP）后观察到的肝脏遗传毒性的机制知之甚少。遗传毒性可能是由于存在转移颗粒，或由于在肺部炎症和急性期反应期间释放的循环炎症介质引起的。为了解决这个问题，我们评估了暴露于二氧化钛（TiO）、氧化铈（CeO）或 CB NP 后对肺部炎症、肺部和肝脏急性期反应以及遗传毒性的诱导作用。雌性 C57BL/6 小鼠通过气管内滴注、静脉注射或口服灌胃接受 162μg NP/小鼠的单次剂量，并在暴露后 1、28 或 180 天与载体对照一起终止。
通过彗星试验评估肝脏 DNA 损伤，在静脉注射和气管内滴注 CB NP 后观察到肝脏 DNA 损伤，但在暴露于 TiO 或 CeO 后没有观察到。NP 气管内暴露导致所有 NP 在暴露后 1 和 28 天的肺部炎症，表现为中性粒细胞流入增加。所有 NP 在三个时间点均检测到持续的肺部急性期反应，而仅观察到短暂的肝脏急性期反应诱导。所有 3 种材料在暴露后 180 天内通过增强暗场显微镜在肝脏中均有检测到。与 TiO 和 CeO NP 相比，CB NP 在非细胞测定中产生 ROS。
我们的结果表明，静脉内和气管内给予 CB NP 后观察到的肝脏 DNA 损伤是由在肝脏中检测到的转移、产生 ROS 的颗粒引起的，而不是由肺部炎症或肝脏急性期反应的继发性影响引起的。
