Li Yun-Cheng, Liu Shu-Yan, Meng Fan-Bing, Xu Shu-Hui, Qiu Jing, Qian Yong-Zhong, Xu Yan-Yang, Li Yun
Institute of Quality Standards and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
College of Food and Biological Engineering, Chengdu University, Chengdu 610106, China.
Foods. 2022 Nov 28;11(23):3848. doi: 10.3390/foods11233848.
Dimethomorph (DMM) is a broad-spectrum fungicide used globally in agricultural production, but little is known regarding the immunotoxicity of DMM in humans. In this study, the immunotoxicity of DMM on human Jurkat T cells was evaluated in vitro. The results indicated that the half-effective concentration (EC) of DMM for Jurkat cells was 126.01 mg/L (0.32 mM). To further elucidate the underlying mechanism, transcriptomics based on RNA sequencing for exposure doses of EC (M21) and EC (L4) was performed. The results indicated that compared to untreated samples (Ctr), 121 genes (81 upregulated, 40 downregulated) and 30 genes (17 upregulated, 13 downregulated) were significantly differentially regulated in the L4 and M21 samples, respectively. A gene ontology analysis indicated that the significantly differentially expressed genes (DEGs) were mostly enriched in the negative regulation of cell activities, and a KEGG pathway analysis indicated that the DEGs were mainly enriched in the immune regulation and signal transduction pathways. A quantitative real-time PCR for the selected genes showed that compared to the high-dose exposure (M21), the effect of the low-dose DMM exposure (L4) on gene expression was more significant. The results indicated that DMM has potential immunotoxicity for humans, and this toxicity cannot be ignored even at low concentrations.
烯酰吗啉（DMM）是一种在全球农业生产中广泛使用的广谱杀菌剂，但关于DMM对人体的免疫毒性知之甚少。在本研究中，体外评估了DMM对人Jurkat T细胞的免疫毒性。结果表明，DMM对Jurkat细胞的半数有效浓度（EC）为126.01 mg/L（0.32 mM）。为进一步阐明潜在机制，对EC（M21）和EC（L4）暴露剂量进行了基于RNA测序的转录组学研究。结果表明，与未处理样本（Ctr）相比，L4和M21样本中分别有121个基因（81个上调，40个下调）和30个基因（17个上调，13个下调）存在显著差异调节。基因本体分析表明，显著差异表达基因（DEG）大多富集于细胞活动的负调控，KEGG通路分析表明，DEG主要富集于免疫调节和信号转导通路。对所选基因进行的定量实时PCR显示，与高剂量暴露（M21）相比，低剂量DMM暴露（L4）对基因表达的影响更显著。结果表明，DMM对人类具有潜在的免疫毒性，即使在低浓度下这种毒性也不容忽视。
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