ABSTRACT
Dichloroacetonitrile (DCAN), an emerged nitrogenous disinfection by-product (N-DBP) in drinking water, has garnered attention owing to its strong cytotoxicity, genotoxicity, and carcinogenicity. However, there are limited studies on its potential hepatotoxicity mechanisms. Understanding hepatotoxicity is essential in order to identify and assess the potential risks posed by environmental pollutants on liver health and to safeguard public health. Here, we investigated the viability, reactive oxygen species (ROS) levels, and cell cycle profile of DCAN-exposed HepG2 cells and analyzed the mechanism of DCAN-induced hepatotoxicity using both transcriptomic and metabolomic techniques. The study revealed that there was a decrease in cell viability, increase in ROS production, and increase in the number of cells in the G2/M phase with an increase in the concentration of DCAN. Omics analyses showed that DCAN exposure increased cellular ROS levels, leading to oxidative damage in hepatocytes, which further induced DNA damage, cell cycle arrest, and cell growth impairment. Thus, DCAN has significant toxic effects on hepatocytes. Integrated analysis of transcriptomics and metabolomics offers new insights into the mechanisms of DCAN-induced hepatoxicity.
Subject(s)
Acetonitriles , Metabolomics , Transcriptome , Humans , Transcriptome/drug effects , Hep G2 Cells , Acetonitriles/toxicity , Water Pollutants, Chemical/toxicity , Reactive Oxygen Species/metabolism , Hepatocytes/drug effects , Hepatocytes/metabolism , Liver/drug effects , Liver/metabolismABSTRACT
@# 长链非编码RNA（lncRNA）是一类长度大于200 nt、且不编码的RNA。lncRNA已被证明与人类疾病紧密相关，尤其 是肿瘤发生发展。研究表明，肿瘤中一些异常表达的lncRNA可以通过不同的信号通路， 如Wnt/β-catenin信号通路，促进肿瘤进 展过程。在不同肿瘤组织中具有特异性表达特征的lncRNA与Wnt/β-catenin信号通路之间的相互作用显示出其作为新的生物标 志物和治疗靶点的潜能。本文就Wnt/β-catenin信号通路相关lncRNA通过调控Wnt/β-catenin信号转导，影响不同肿瘤类型发生 发展的作用进行综述。本文结果或可为临床肿瘤诊断和治疗提供新的思路。