The industrial and agricultural applications of rare earth elements (REEs) lead to considerable REE emissions into environment. Yet, little is known about the molecular-level effects and interactions of REEs in terrestrial plants. Herein, the individual and joint effects of La and Ce in Triticum aestivum were investigated using mass spectrometry-based metabolomics. Metabolic effect level index (MELI) was utilized as a readable endpoint for quantifying mixture interactions. Exposure to single La/Ce at environmentally relevant levels induced significant dose-dependent metabolic changes. The highly overlap of differential metabolites and perturbed pathways of La and Ce suggested their similar mode of action. Exposure to La-Ce mixtures did not induce additional metabolic pathway perturbation. Specifically, metabolism of amino sugar and nucleotide sugar, starch and sucrose, fructose and mannose, glycerophospholipid and purine were disrupted for both single and binary exposures. These results, together with physiological indicators, point to REE-induced oxidative stress, energy expenditure, DNA damage and membrane disturbance. The MELI calculations showed that La and Ce interacted synergistically at the overall metabolic level, which could be causally linked to synergistic interaction at the individual level (root elongation). This work proved metabolomics could be an important and effective strategy for interpreting toxicity and interactions of REE mixtures.

稀土元素 (REE) 的工业和农业应用导致大量 REE 排放到环境中。然而，人们对陆生植物中稀土元素的分子水平效应和相互作用知之甚少。在此，La和Ce在普通小麦中的个体和联合作用使用基于质谱的代谢组学研究。代谢效应水平指数 (MELI) 被用作量化混合物相互作用的可读端点。暴露于环境相关水平的单一 La/Ce 会引起显着的剂量依赖性代谢变化。差异代谢物的高度重叠和 La 和 Ce 的扰动途径表明它们的作用方式相似。暴露于 La-Ce 混合物不会引起额外的代谢途径扰动。具体而言，单次和二元暴露都会破坏氨基糖和核苷酸糖、淀粉和蔗糖、果糖和甘露糖、甘油磷脂和嘌呤的代谢。这些结果与生理指标一起，指向 REE 诱导的氧化应激、能量消耗、DNA 损伤和膜紊乱。MELI 计算表明，La 和 Ce 在整体代谢水平上协同相互作用，这可能与个体水平上的协同相互作用（根伸长）有因果关系。这项工作证明代谢组学可能是解释 REE 混合物的毒性和相互作用的重要且有效的策略。