尿素类是由水稻假黑穗病的代谢产生的一种霉菌毒素。研究表明,尿素类可能对动物有毒,但是仍然缺乏毒理学证据。肝脏,作为外来化学品生物转化的主要器官,可能是尿霉素毒性的直接靶器官。在这项研究中,我们发现,当BNLCL.2细胞用不同浓度的尿素类(0、5、10、20、30、40、60、80、100、150和200μg/mL)处理24和48小时时,细胞活力以剂量和时间依赖性方式降低。扫描电镜观察显示实验组细胞膜受损,随着凋亡体的出现。此外,暴露于尿素类的细胞中ROS和GSH水平显著升高。我们使用全长转录组学分析了尿素类对肝细胞损伤的关键作用靶标。共筛选出1099个差异表达基因,其中473个基因上调,626个基因下调。此外,我们还发现,用尿素类处理的BNLCL.2细胞中MCM7和CDC45的表达降低,根据qRT-PCR,CC1-2,CYP1b1,CYP4f13和GSTM1的表达增加。尿素类可能改变CYP450和GST相关基因,影响DNA复制和细胞周期,并导致氧化应激和肝细胞损伤。
Ustiloxins is a mycotoxin produced by the metabolism of Rice false smut. Studies have shown that Ustiloxins may be toxic to animals, but there is still a lack of toxicological evidence. The liver, as the main organ for the biotransformation of foreign chemicals, may be the direct target organ of Ustiloxins toxicity. In this
study, we found that cell viability decreased in a dose- and time-dependent manner when BNL CL.2 cells were treated with different concentrations of Ustiloxins (0, 5, 10, 20, 30, 40, 60, 80, 100, 150 and 200 μg/mL) for 24 and 48 h. In addition, scanning electron microscope observation showed that the cell membrane of the experimental group was damaged, with the appearance of apoptotic bodies. Moreover, the ROS and GSH levels were significantly increased in cells exposed to Ustiloxins. We analyzed the key action targets of Ustiloxins on hepatocyte injury using full-length transcriptomics. A total of 1099 differentially expressed genes were screened, of which 473 genes were up-regulated, and 626 genes were down-regulated. Besides, we also found that the expression of MCM7 and CDC45 in BNL CL.2 cells treated with Ustiloxins decreased, and the expression of CCl-2, CYP1b1, CYP4f13, and GSTM1 increased according to qRT-PCR. Ustiloxins might change CYP450 and GST-related genes, affect DNA replication and cell cycle, and lead to oxidative stress and liver cell injury.