Wang Ning
Institute of Chemical Toxicity Testing/NHC Specialty Laboratory of Food, Safety Risk Assessment and Standard Development/State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.
Front Pharmacol. 2024 Dec 17;15:1484111. doi: 10.3389/fphar.2024.1484111. eCollection 2024.
Neodymium, a rare earth element, has been shown to induce genotoxicity in mice, but the molecular mechanisms behind this effect are not fully understood. This study aims to investigate the genotoxic effects of intragastric administration of neodymium nitrate (Nd(NO)) over 28 consecutive days and to elucidate the underlying molecular mechanisms.
We detected the content of neodymium in mouse liver tissue using ICP-MS and assessed the percentage of tail DNA in mouse hepatocytes using the alkaline comet assay to evaluate genotoxicity. Additionally, we evaluated genetic toxicological biomarkers (reactive oxygen species (ROS), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and γ-H2AX) and the expression levels of genes related to the p53 pathway in the mouse liver.
Our findings indicate a potential accumulation of (Nd(NO)) in the livers of mice, leading to DNA double-strand breaks in hepatocytes, as evidenced by comet and γ-H2AX assays. Nd(NO3)3 significantly increased the percentage of tail DNA in hepatocytes and upregulated the expression of molecules related to the p53 pathway, including ATM, Wip1, ATR, Chk2, MDM2, p53, p21, and NF-κB, at the transcriptional level. The treatment also effectively triggered the production of ROS, 8-OHdG, and γ-H2AX in liver tissue.
These results suggest that (Nd(NO)) induces hepatic genotoxicity and injury in mice and modulates the expression of genes associated with DNA damage response, carcinogenesis, and inflammatory processes. The study provides insights into the molecular mechanisms by which neodymium nitrate exerts its genotoxic effects and underscores the importance of further investigating the potential health risks associated with neodymium exposure.
钕是一种稀土元素，已被证明可在小鼠中诱发基因毒性，但其背后的分子机制尚未完全明确。本研究旨在探究连续28天经胃内给予硝酸钕（Nd(NO₃)₃）的基因毒性效应，并阐明其潜在的分子机制。
我们使用电感耦合等离子体质谱法（ICP-MS）检测小鼠肝脏组织中的钕含量，并采用碱性彗星试验评估小鼠肝细胞中尾部DNA的百分比，以评估基因毒性。此外，我们还评估了基因毒理学生物标志物（活性氧（ROS）、8-羟基-2'-脱氧鸟苷（8-OHdG）和γ-H2AX）以及小鼠肝脏中与p53通路相关基因的表达水平。
我们的研究结果表明，（Nd(NO₃)₃）可能在小鼠肝脏中蓄积，导致肝细胞中的DNA双链断裂，彗星试验和γ-H2AX试验证明了这一点。Nd(NO₃)₃显著增加了肝细胞中尾部DNA的百分比，并在转录水平上调了与p53通路相关分子的表达，包括ATM、Wip1、ATR、Chk2、MDM2、p53、p21和NF-κB。该处理还有效触发了肝脏组织中ROS、8-OHdG和γ-H2AX的产生。
这些结果表明，（Nd(NO₃)₃）可诱导小鼠肝脏基因毒性和损伤，并调节与DNA损伤反应、致癌作用和炎症过程相关的基因表达。该研究为硝酸钕发挥其基因毒性作用的分子机制提供了见解，并强调了进一步研究与钕暴露相关潜在健康风险的重要性。
