Chemical carcinogenicity of neodymium nitrate in AML12 hepatocytes: Dose-response metabolomics and sensitive biomarker identification

This study aims to investigate the chemical carcinogenic toxicity of neodymium nitrate (Nd(NO₃)₃) in mouse hepatocytes AML12 using dose-response metabolomics. Specifically, our objectives are to: Identify key metabolites that respond to Nd(NO₃)₃ exposure. Elucidate the mechanisms underlying Nd(NO₃)₃-induced liver toxicity. Provide a scientific basis for risk assessment of Nd(NO₃)₃ exposure. AML12 cells were exposed to different concentrations of Nd(NO₃)₃ (0, 0.2, 0.4, and 0.8 µM) for 24 h. Metabolite changes were analyzed using UPLC-MS, and differential metabolites (DMs) were identified. Key metabolic pathways affected by Nd(NO₃)₃ include amino acid metabolism, nucleotide metabolism, and energy metabolism. Significant changes in these pathways suggest that Nd(NO₃)₃ induces metabolic disturbances that may lead to cytotoxicity. We identified potential biomarkers, such as UDP-N-acetylglucosamine, L-glutathione, and glycine, which exhibit dose-dependent responses. These findings provide insights into the mechanisms of Nd(NO₃)₃-induced chemical carcinogenicity and offer a scientific basis for risk assessment. Future research should further explore the toxicity and mechanisms in in vivo settings. CONCLUSION: Our study reveals that Nd(NO₃)₃ induces metabolic disturbances in AML12 hepatocytes, leading to potential cytotoxicity. The identified potential biomarkers, such as UDP-N-acetylglucosamine, L-glutathione, and glycine, provide a basis for early detection and risk assessment of Nd(NO₃)₃ exposure. Further in vivo studies are needed to explore the long-term effects and mechanisms of Nd(NO₃)₃ toxicity.