Navarrete Julian, Wilson Peyton, Allsing Nicholas, Gordon Chandi, Margolis Rachel, Schwartz Ashley V, Cho Christine, Rogowski Brynn, Topps Jennifer, George Uduak Z, Sant Karilyn E
San Diego State University School of Public Health, 5500 Campanile Dr., Hardy Tower 119, San Diego, CA, 92182, USA.
San Diego State University Biology Department, San Diego, CA, 92182, USA.
Aquat Toxicol. 2021 Jun;235:105815. doi: 10.1016/j.aquatox.2021.105815. Epub 2021 Mar 26.
Tris(4-chlorophenyl)methanol (TCPMOH) is a water contaminant with unknown etiology, but is believed to be a byproduct of DDT manufacturing. It is highly persistent in the environment, and bioaccumulates in marine species. TCPMOH has also been measured in human breast milk, which poses a risk for developing infants. However, almost no toxicity data is currently available. In this study, we investigate the hazard posed by developmental TCPMOH exposures using the zebrafish model (Danio rerio). Zebrafish (Danio rerio) embryos were exposed to 0, 0.1, 0.5, 1, or 5 µM TCPMOH beginning at 24 h post fertilization (hpf). Embryonic mortality and incidence of morphological deformities increased in a concentration-dependent manner with TCPMOH exposure. RNA sequencing assessed changes in gene expression associated with acute (4 hour) exposures to 50 nM TCPMOH. Developmental exposure to TCPMOH decreased expression of ahr2, as well as metabolic enzymes cyp1a1, cyp1b1, cyp1c1, cyp1c2, and cyp2y3 (p<0.05). These findings were concordant with decreased Cyp1a1 induction measured by the ethoxyresorufin-O-deethylase (EROD) assay (p<0.05). Pathways associated with xenobiotic metabolism, lipid metabolism, and transcriptional and translational regulation were decreased. Pathways involved in DNA replication and repair, carbohydrate metabolism, and endocrine function were upregulated. Overall, this study demonstrates that TCPMOH is acutely toxic to zebrafish embryos at elevated concentrations.
三(4-氯苯基)甲醇(TCPMOH)是一种病因不明的水体污染物,但被认为是滴滴涕制造过程中的副产物。它在环境中具有高度持久性,并在海洋物种中生物累积。在人类母乳中也检测到了TCPMOH,这对发育中的婴儿构成了风险。然而,目前几乎没有毒性数据。在本研究中,我们使用斑马鱼模型(Danio rerio)研究发育过程中TCPMOH暴露所带来的危害。斑马鱼(Danio rerio)胚胎在受精后24小时(hpf)开始暴露于0、0.1、0.5、1或5μM的TCPMOH中。随着TCPMOH暴露,胚胎死亡率和形态畸形发生率呈浓度依赖性增加。RNA测序评估了与急性(4小时)暴露于50 nM TCPMOH相关的基因表达变化。发育过程中暴露于TCPMOH会降低ahr2以及代谢酶cyp1a1、cyp1b1、cyp1c1、cyp1c2和cyp2y3的表达(p<0.05)。这些发现与通过乙氧基异吩恶唑酮-O-脱乙基酶(EROD)测定法测得的Cyp1a1诱导降低一致(p<0.05)。与异生物质代谢、脂质代谢以及转录和翻译调控相关的通路减少。参与DNA复制和修复、碳水化合物代谢以及内分泌功能的通路上调。总体而言,本研究表明,高浓度的TCPMOH对斑马鱼胚胎具有急性毒性。