The coexistence of nanoplastics (NPs) and various pollutants in the marine environment has become a problem that cannot be ignored. NPs and marine algae toxins are found in marine organisms and both can enter the human body through the food chain. However, the joint toxic effects of marine algae toxins and NPs on human health remain unknown. In this study, the joint toxic effects and mechanisms of polystyrene (PS) NPs and okadaic acid (OA) were investigated on human gastric adenocarcinoma (AGS) cells. AGS cells were exposed to 20 nm PS (0.5, 8 μg mL⁻¹) or/and OA (5, 10 ng mL⁻¹), and their cytotoxicity was assessed by measuring relevant indicators, transcriptomics, and weighted gene co-expression network analysis (WGCNA). Our data indicated that the joint toxicity of PS and OA to AGS cells was mainly characterized by a decrease in cell viability, depolarization of mitochondrial membrane potential, and a decrease in IL10 and p53 protein activity, accompanied by an increase in intracellular ROS production and calcium and IL8 levels in comparison with single contaminants. In addition, co-exposure to PS and OA caused cellular damage by activating PI3K/AKT, ERK/c-FOS and caspase-3/caspase-9 signaling pathways. Moreover, the high concentration of PS significantly enhanced the toxicity of OA. WGCNA highlighted enrichment in the Fanconi anemia pathway and MAPK signaling pathway and identified that IER3 was the hub gene in PS and OA co-exposed AGS cells. The results of this study provided insights into the joint toxicity evaluation of NPs and marine algae toxins.

中文翻译：

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聚苯乙烯纳米塑料是否会加重单一污染物（冈田酸）的毒性？使用 AGS 细胞作为生物模型

纳米塑料（NPs）与海洋环境中的各种污染物共存已成为一个不容忽视的问题。纳米颗粒和海藻毒素存在于海洋生物中，两者都可以通过食物链进入人体。然而，海藻毒素和纳米颗粒对人类健康的联合毒性作用仍然未知。在这项研究中，研究了聚苯乙烯 (PS) NPs 和冈田酸 (OA) 对人胃腺癌细胞 (AGS) 的联合毒性作用和机制。AGS 细胞暴露于 20 nm PS (0.5, 8 μg mL ^-1 ) 或/和 OA (5, 10 ng mL ^-1)，并通过测量相关指标、转录组学和加权基因共表达网络分析 (WGCNA) 来评估它们的细胞毒性。我们的数据表明，PS 和 OA 对 AGS 细胞的联合毒性主要表现为细胞活力降低、线粒体膜电位去极化、IL10 和 p53 蛋白活性降低，伴随细胞内 ROS 产生和钙离子增加。和 IL8 水平与单一污染物相比。此外，同时暴露于 PS 和 OA 通过激活 PI3K/AKT、ERK/c-FOS 和 caspase-3/caspase-9 信号通路引起细胞损伤。此外，高浓度的 PS 显着增强了 OA 的毒性。WGCNA 强调了 Fanconi 贫血通路和 MAPK 信号通路的富集，并确定了IER3是 PS 和 OA 共同暴露的 AGS 细胞中的中枢基因。这项研究的结果为纳米颗粒和海藻毒素的联合毒性评估提供了见解。