由于三氯卡班（TCC）作为广谱杀菌剂的高频使用，其暴露已引起对水生生物和人体健康的极大关注。我们基于斑马鱼转录组测序数据分析，确认了TCC通过调控相关基因的转录调控诱导氧化应激和免疫功能失调。利用癌症基因组图谱数据库（TCGA）组装程序筛选出52个与免疫功能相关的常见差异表达基因，这些基因与胰腺癌样本数据的元分析和TCC暴露幼鱼的差异转录谱有关。急性TCC暴露对天然免疫细胞的形成、成熟胸腺T细胞发育受到延迟、免疫球蛋白M水平降低并促进过量释放促炎症因子（IL-6、IL-1β和tnfα）。在TCC暴露下，与胰腺癌免疫细胞丰度相关的基因表达明显下调，与此同时ROS水平显著增加，抗氧化活性明显下降。而且，在暴露TCC的情况下，PI3K/Nrf2抗氧化应激途径中的一系列标志基因（pi3k、nrf2、keap1、ho-1和nqo1）异常表达。有趣的是，维生素C减少了120小时后期幼鱼的畸形，提高了存活率，并有效缓解了TCC引起的氧化应激和免疫反应。总的来说，TCC暴露抑制了PI3K/Nrf2信号途径的抗氧化能力，引起免疫毒性，并增加了胰腺癌的风险，这些观察结果丰富了我们对TCC对斑马鱼早期胚胎和幼体发育以及免疫损伤的深入理解。版权所有©2023 Elsevier Ltd.

Owing to frequent application as a broad-spectrum bactericide, triclocarban (TCC) exposure has raised great concern for aquatic organisms and human health. Herein, based on transcriptome sequencing data analysis of zebrafish, we confirmed that TCC induced oxidative stress and dysimmunity through transcriptional regulation of the related genes. With aid of the Cancer Genome Atlas (TCGA) assembler database, 52 common differentially expressed genes, whose functions were related to immunity, were screened out by virtue of the meta-analysis of pancreatic cancer sample data and differential transcription profiles from TCC-exposed larvae. Acute TCC exposure affected formation of the innate immune cells, delayed mature thymic T-cell development, reduced immunoglobulin M (IgM) levels and promoted excessive release of the pro-inflammatory factors (IL-6, IL-1β and tnfα). Under TCC exposure, the expressions of the genes associated with immune cell abundance in pancreatic cancer were significantly down-regulated, while the levels of ROS were prominently increased in concomitant with suppressed antioxidant activity. Moreover, a series of marker genes (pi3k, nrf2, keap1, ho-1 and nqo1) in the PI3K/Nrf2 antioxidant-stress pathway were abnormally expressed under TCC exposure. Interestingly, vitamin C decreased the malformation and increased the survival rate of 120-hpf larvae and effectively alleviated TCC-induced oxidative stress and immune responses. Overall, TCC exposure induced immunotoxicity and increased the risk of pancreatic cancer by inhibiting the antioxidant capacity of the PI3K/Nrf2 signal pathway. These observations enrich our in-depth understanding of the effects of TCC on early embryonic-larval development and immune damage in zebrafish.Copyright © 2023. Published by Elsevier Ltd.