Immunotoxicity induced by triclocarban exposure in zebrafish triggering the risk of pancreatic cancer

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-18 and tnf alpha). 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.

Automated summary

Based on transcriptome sequencing data analysis of zebrafish, it was confirmed that triclocarban (TCC) exposure induced oxidative stress and dysimmunity through transcriptional regulation of related genes. Pancreatic cancer sample data and differential transcription profiles were analyzed to identify 52 common differentially expressed genes related to immunity in TCC-exposed larvae. TCC exposure affected immune cell development, reduced immunoglobulin levels, promoted excessive release of pro-inflammatory factors, and inhibited antioxidant activity, increasing the risk of pancreatic cancer.