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Comparative Transcriptome Analysis to Investigate the Immunotoxicity Mechanism Triggered by Dimethomorph on Human
Yun-Cheng Li1,2, Shu-Yan Liu2, Fan-Bing Meng2
1Institute of Quality Standards and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
Abstract:
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 (EC50) 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 EC25 (M21) and EC10 (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.
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