National Research Centre for the Working Environment, Copenhagen, Denmark.
Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen, Denmark.
Nanotoxicology. 2022 May;16(4):526-546. doi: 10.1080/17435390.2022.2106906. Epub 2022 Aug 22.
Carbon black nanoparticles (CBNPs) have a large surface area/volume ratio and are known to generate oxidative stress and inflammation that may result in genotoxicity and cancer. Here, we evaluated the primary and inflammatory response-driven (i.e. secondary) genotoxicity of two CBNPs, Flammruss101 (FL101) and PrintexXE2B (XE2B) that differ in size and specific surface area (SSA), and cause different amounts of reactive oxygen species. Three doses (low, medium and high) of FL101 and XE2B were assessed in the lung epithelial (A549) and activated THP-1 (THP-1a) monocytic cells exposed in submerged conditions for 6 and 24 h, and in C57BL/6 mice at day 1, 28 and 90 following intratracheal instillation. , we assessed pro-inflammatory response as IL-8 and IL-1β gene expression, and , inflammation was determined as inflammatory cell infiltrates in bronchial lavage (BAL) fluid and as histological changes in lung tissue. DNA damage was quantified and as DNA strand breaks levels by the alkaline comet assay. Inflammatory responses and correlated with dosed CBNPs SSA. Both materials induced DNA damage in THP-1a (correlated with dosed mass), and only XE2B in A549 cells. Non-statistically significant increase in DNA damage was observed in BAL cells. In conclusion, this study shows dosed SSA predicted inflammation and , whereas dosed mass predicted genotoxicity in THP-1a cells. The observed lack of correlation between CBNP surface area and genotoxicity provides little evidence of inflammation-driven genotoxicity and .
碳黑纳米颗粒(CBNPs)具有较大的表面积/体积比,已知会产生氧化应激和炎症,从而导致遗传毒性和癌症。在这里,我们评估了两种 CBNPs(Flammruss101(FL101)和 PrintexXE2B(XE2B))的原发性和炎症反应驱动(即继发性)遗传毒性,它们在尺寸和比表面积(SSA)上有所不同,并导致产生不同数量的活性氧。在 6 和 24 小时的浸浴条件下,在肺上皮(A549)和激活的 THP-1(THP-1a)单核细胞中评估了三种剂量(低、中、高)的 FL101 和 XE2B,并且在气管内滴注后第 1、28 和 90 天的 C57BL/6 小鼠中进行了评估。我们评估了促炎反应,如 IL-8 和 IL-1β 基因表达,并且,炎症通过支气管肺泡灌洗液(BAL)中的炎症细胞浸润和肺组织的组织学变化来确定。通过碱性彗星试验定量和评估 DNA 损伤水平。炎症反应和与 CBNPs 的剂量 SSA 相关。两种材料都在 THP-1a 细胞中诱导了 DNA 损伤(与剂量质量相关),而仅在 A549 细胞中诱导了 XE2B。在 BAL 细胞中观察到 DNA 损伤的非统计学显著增加。总之,本研究表明,剂量 SSA 预测了炎症和,而剂量质量预测了 THP-1a 细胞的遗传毒性。观察到 CBNP 表面积与遗传毒性之间缺乏相关性,这提供了炎症驱动的遗传毒性的证据很少。