Humans are exposed to multiple exogenous substances, notably through food consumption. Many of these compounds are suspected to impact human health, and their combination could exacerbate their harmful effects. We previously observed in human cells that, among the six most prevalent food contaminant complex mixtures identified in the French diet, synergistic interactions between component appeared in two mixtures compared with the response with the chemicals alone. In the present study, we demonstrated in human cells that these properties are driven only by two heavy metals in each mixture: tellurium (Te) with cadmium (Cd) and Cd with inorganic arsenic (As), respectively. It appeared that the predicted effects for these binary mixtures using the mathematical model of Chou and Talalay confirmed synergism between these heavy metals. Based on different cell biology experiments (cytotoxicity, genotoxicity, mutagenesis and DNA repair inhibition experiments), a detailed mechanistic analysis of these two mixtures suggests that concomitant induction of oxidative DNA damage and decrease of their repair capacity contribute to the synergistic toxic effect of these chemical mixtures. Overall, these results may have broad implications for the fields of environmental toxicology and chemical mixture risk assessment.

中文翻译：

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食品污染物混合物对人体细胞的协同毒性作用。


人类接触多种外源物质，特别是通过食物消费。其中许多化合物被怀疑会影响人类健康，它们的组合可能会加剧其有害影响。我们之前在人体细胞中观察到，在法国饮食中发现的六种最常见的食品污染物复合混合物中，与单独使用化学物质的反应相比，两种混合物中的成分之间出现了协同相互作用。在本研究中，我们在人体细胞中证明，这些特性仅由每种混合物中的两种重金属驱动：分别是碲 (Te) 与镉 (Cd) 以及镉与无机砷 (As)。使用 Chou 和 Talalay 的数学模型对这些二元混合物的预测效果似乎证实了这些重金属之间的协同作用。基于不同的细胞生物学实验（细胞毒性、基因毒性、诱变和 DNA 修复抑制实验），对这两种混合物的详细机制分析表明，同时诱导氧化 DNA 损伤并降低其修复能力，导致这些化学物质的协同毒性作用混合物。总体而言，这些结果可能对环境毒理学和化学混合物风险评估领域具有广泛的影响。