Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
Toxins (Basel). 2022 May 25;14(6):368. doi: 10.3390/toxins14060368.
Aflatoxin B1 (AFB1) is a common crop contaminant, while aflatoxin M1 (AFM1) is implicated in milk safety. Humans are likely to be simultaneously exposed to AFB1 and AFM1; however, studies on the combined interactive effects of AFB1 and AFM1 are lacking. To fill this knowledge gap, transcriptomic, proteomic, and microRNA (miRNA)-sequencing approaches were used to investigate the toxic mechanisms underpinning combined AFB1 and AFM1 actions in vitro. Exposure to AFB1 (1.25-20 μM) and AFM1 (5-20 μM) for 48 h significantly decreased cell viability in the intestinal cell line, NCM460. Multi-omics analyses demonstrated that additive toxic effects were induced by combined AFB1 (2.5 μM) and AFM1 (2.5 μM) in NCM460 cells and were associated with p53 signaling pathway, a common pathway enriched by differentially expressed mRNAs/proteins/miRNAs. Specifically, based on p53 signaling, cross-omics showed that AFB1 and AFM1 reduced NCM460 cell viability via the hsa-miR-628-3p- and hsa-miR-217-5p-mediated regulation of cell surface death receptor (FAS), and also the hsa-miR-11-y-mediated regulation of cyclin dependent kinase 2 (CDK2). We provide new insights on biomarkers which reflect the cytotoxic effects of combined AFB1 and AFM1 toxicity.
黄曲霉毒素 B1（AFB1）是一种常见的农作物污染物，而黄曲霉毒素 M1（AFM1）与牛奶安全有关。人类可能同时接触到 AFB1 和 AFM1；然而，目前缺乏关于 AFB1 和 AFM1 联合交互作用的研究。为了填补这一知识空白，采用转录组学、蛋白质组学和 microRNA（miRNA）测序方法，研究了体外联合 AFB1 和 AFM1 作用下的毒性机制。暴露于 AFB1（1.25-20 μM）和 AFM1（5-20 μM）48 h 显著降低了肠细胞系 NCM460 的细胞活力。多组学分析表明，AFB1（2.5 μM）和 AFM1（2.5 μM）联合作用于 NCM460 细胞时会产生附加的毒性作用，与 p53 信号通路有关，该通路是差异表达的 mRNAs/蛋白质/miRNAs 富集的常见通路。具体而言，基于 p53 信号通路，交叉组学表明 AFB1 和 AFM1 通过 hsa-miR-628-3p 和 hsa-miR-217-5p 介导的细胞表面死亡受体（FAS）的调节，以及 hsa-miR-11-y 介导的细胞周期蛋白依赖性激酶 2（CDK2）的调节，降低了 NCM460 细胞的活力。我们提供了新的见解，反映了联合 AFB1 和 AFM1 毒性的细胞毒性作用的生物标志物。
