National Center of Biomedical Analysis, Beijing 100850, China.
Toxins (Basel). 2021 May 27;13(6):384. doi: 10.3390/toxins13060384.
Hepatitis B virus (HBV) infection and aflatoxin B1 (AFB1) exposure have been recognized as independent risk factors for the occurrence and development of hepatocellular carcinoma (HCC), but their combined impacts and the potential metabolic mechanisms remain poorly characterized. Here, a comprehensive non-targeted metabolomic study was performed following AFB1 exposed to Hep3B cells at two different doses: 16 μM and 32 μM. The metabolites were identified and quantified by an ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based strategy. A total of 2679 metabolites were identified, and 392 differential metabolites were quantified among three groups. Pathway analysis indicated that dynamic metabolic reprogramming was induced by AFB1 and various pathways changed significantly, including purine and pyrimidine metabolism, hexosamine pathway and sialylation, fatty acid synthesis and oxidation, glycerophospholipid metabolism, tricarboxylic acid (TCA) cycle, glycolysis, and amino acid metabolism. To the best of our knowledge, the alteration of purine and pyrimidine metabolism and decrease of hexosamine pathways and sialylation with AFB1 exposure have not been reported. The results indicated that our metabolomic strategy is powerful to investigate the metabolome change of any stimulates due to its high sensitivity, high resolution, rapid separation, and good metabolome coverage. Besides, these findings provide an overview of the metabolic mechanisms of the AFB1 combined with HBV and new insight into the toxicological mechanism of AFB1. Thus, targeting these metabolic pathways may be an approach to prevent carcinogen-induced cancer, and these findings may provide potential drug targets for therapeutic intervention.
乙型肝炎病毒（HBV）感染和黄曲霉毒素 B1（AFB1）暴露已被认为是肝细胞癌（HCC）发生和发展的独立危险因素，但它们的联合影响和潜在代谢机制仍知之甚少。在这里，我们采用一种全面的非靶向代谢组学研究方法，在两种不同剂量（16 μM 和 32 μM）的 AFB1 暴露下对 Hep3B 细胞进行研究。采用超高效液相色谱-质谱（UPLC-MS）为基础的策略对代谢物进行鉴定和定量。共鉴定出 2679 种代谢物，在三组之间定量了 392 种差异代谢物。通路分析表明，AFB1 诱导了动态代谢重编程，多种通路发生了显著变化，包括嘌呤和嘧啶代谢、己糖胺途径和唾液酸化、脂肪酸合成和氧化、甘油磷脂代谢、三羧酸（TCA）循环、糖酵解和氨基酸代谢。据我们所知，AFB1 暴露引起的嘌呤和嘧啶代谢改变以及己糖胺途径和唾液酸化的减少尚未有报道。结果表明，我们的代谢组学策略由于其高灵敏度、高分辨率、快速分离和良好的代谢组覆盖范围，是研究任何刺激物代谢组变化的有力工具。此外，这些发现为 AFB1 与 HBV 联合作用的代谢机制提供了全面的概述，并为 AFB1 的毒理学机制提供了新的见解。因此，针对这些代谢途径可能是预防致癌物诱导癌症的一种方法，这些发现可能为治疗干预提供潜在的药物靶点。
