Nanomaterial Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), VishvigyanBhawan, 31, M.G. Marg, PO Box 80, Lucknow, Uttar Pradesh 226001, India.
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
Mutagenesis. 2022 Apr 2;37(1):44-59. doi: 10.1093/mutage/geac005.
Incessant production, pervasive applications in different fields, and eventually unintended exposure of cobalt oxide nanoparticles (Co3O4 NPs) lead to rise in their toxicity studies toward human health. However, the information regarding the potential toxicity mechanisms of Co3O4 NPs especially genotoxicity is still sparse with missing interconnections. So far, only solitary reports on Co3O4 NPs are at hand, bearing witness to reactive oxygen species (ROS)-mediated DNA damage in lung cells. To address this, we evaluated the Co3O4 NP-induced cytotoxic and genotoxic potential in Chinese hamster lung fibroblast cell line (V79). Our preliminary results demonstrate that Co3O4 NPs at concentrations of 20-100 µg/ml induced moderate mortality after 24-h exposure. However, these low concentrations caused a significant reduction in various organelles' activity in a concentration-dependent manner. Mitochondrial activity and membrane potential were found to be compromised due to NP exposure in a concentration-dependent manner. The study affirms that Co3O4 NPs inhibited lysosomal activity in V79 cells. In addition to this, Co3O4 NPs are also found to stimulate free oxygen radical generation. Genotoxicity studies revealed a potent and dose-dependent effect of non-cytotoxic concentrations of Co3O4 NPs in the induction of DNA lesions. Interestingly, N-acetylcysteine, a free oxygen radical scavenger (5, 10 mM, pretreatment) inhibited the progression of free oxygen radicals and induction of Co3O4 NP-mediated DNA lesions. This suggests the ROS-mediated genotoxic potential of Co3O4 NPs.
不断的生产、在不同领域的广泛应用，以及最终钴氧化物纳米粒子（Co3O4 NPs）的意外暴露，导致了人们对其人类健康毒性的研究增加。然而，关于 Co3O4 NPs 的潜在毒性机制，特别是遗传毒性的信息仍然很少，而且缺乏相互联系。到目前为止，只有关于 Co3O4 NPs 的单独报道，证明了其在肺细胞中通过活性氧物质（ROS）介导的 DNA 损伤。为了解决这个问题，我们评估了 Co3O4 NP 在中华仓鼠肺成纤维细胞系（V79）中诱导的细胞毒性和遗传毒性潜力。我们的初步结果表明，Co3O4 NPs 在 20-100µg/ml 的浓度下，暴露 24 小时后会引起中等程度的死亡率。然而，这些低浓度会导致各种细胞器的活性以浓度依赖的方式显著降低。由于 NP 暴露，线粒体活性和膜电位也被发现以浓度依赖的方式受到损害。该研究证实 Co3O4 NPs 抑制了 V79 细胞中的溶酶体活性。除此之外，Co3O4 NPs 还被发现刺激了游离氧自由基的生成。遗传毒性研究显示，非细胞毒性浓度的 Co3O4 NPs 对 DNA 损伤具有强大的、剂量依赖的效应。有趣的是，游离氧自由基清除剂 N-乙酰半胱氨酸（5、10 mM，预处理）抑制了游离氧自由基的进展和 Co3O4 NP 介导的 DNA 损伤的诱导。这表明 Co3O4 NPs 具有 ROS 介导的遗传毒性潜力。
