Differences in inflammation and acute phase response but similar genotoxicity in mice following pulmonary exposure to graphene oxide and reduced graphene oxide.
Differences in inflammation and acute phase response but similar genotoxicity in mice following pulmonary exposure to graphene oxide and reduced graphene oxide.
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DOI：
10.1371/journal.pone.0178355
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Vogel U
中科院分区：
文献类型：
--
作者：
Bengtson S;Knudsen KB;Kyjovska ZO;Berthing T;Skaug V;Levin M;Koponen IK;Shivayogimath A;Booth TJ;Alonso B;Pesquera A;Zurutuza A;Thomsen BL;Troelsen JT;Jacobsen NR;Vogel U
我们研究了2-3层>1 μm尺寸的氧化石墨烯（GO）和还原氧化石墨烯（rGO）在小鼠中单次气管内暴露后的毒性，包括肺部炎症、急性期反应（心血管疾病风险的生物标志物）和遗传毒性。此外，我们评估了在洁净室和使用化学气相沉积的正常工业环境中生产石墨烯期间排放的颗粒物的暴露水平。在第1、3、28和90天（18、54和162 μg/小鼠）评价毒性，但在第28和90天仅评价了GO暴露小鼠的最低剂量。GO诱导强烈的急性炎症反应以及肺（血清淀粉样蛋白A，Saa 3）和肝（Saa 1）急性期反应。rGO诱导的急性程度较低，但炎症持续且延长至第90天。肺组织病理学在第90天显示颗粒聚集，无纤维化迹象。此外，在GO和rGO的时间点和剂量范围内观察到BAL细胞中的DNA损伤。总之，肺暴露于GO和rGO诱导炎症，急性期反应和遗传毒性，但没有纤维化。
We investigated toxicity of 2–3 layered >1 μm sized graphene oxide (GO) and reduced graphene oxide (rGO) in mice following single intratracheal exposure with respect to pulmonary inflammation, acute phase response (biomarker for risk of cardiovascular disease) and genotoxicity. In addition, we assessed exposure levels of particulate matter emitted during production of graphene in a clean room and in a normal industrial environment using chemical vapour deposition. Toxicity was evaluated at day 1, 3, 28 and 90 days (18, 54 and 162 μg/mouse), except for GO exposed mice at day 28 and 90 where only the lowest dose was evaluated. GO induced a strong acute inflammatory response together with a pulmonary (Serum-Amyloid A, Saa3) and hepatic (Saa1) acute phase response. rGO induced less acute, but a constant and prolonged inflammation up to day 90. Lung histopathology showed particle agglomerates at day 90 without signs of fibrosis. In addition, DNA damage in BAL cells was observed across time points and doses for both GO and rGO. In conclusion, pulmonary exposure to GO and rGO induced inflammation, acute phase response and genotoxicity but no fibrosis.