The commonly used antimicrobial additive triclosan is a liver tumor promoter

Abstract

Significance Triclosan [5-chloro-2-(2,4-dichlorophenoxy)phenol; TCS] is a broad-spectrum antimicrobial agent that has become one of the most common additives used in consumer products. As a result, TCS has significantly affected the environment and has been frequently detected in human body fluids. Through a long-term feeding study, we found that TCS enhances hepatocyte proliferation, fibrogenesis, and oxidative stress, which, we believe, can be the driving force for developing advanced liver disease in mice. Indeed, TCS strongly enhances hepatocarcinogenesis after diethylnitrosamine initiation, accelerating hepatocellular carcinoma (HCC) development. Although animal studies require higher chemical concentrations than predicted for human exposure, this study demonstrates that TCS acts as a HCC tumor promoter and that the mechanism of TCS-induced mouse liver pathology may be relevant to humans.

Influence of temperature on thyroid hormone signaling and endocrine disruptor action in Rana (Lithobates) catesbeiana tadpoles

“…However, evidence for other mechanisms involving impact on transcription factor activity exists (Stuhlmeier et al, 1999;Tegeder et al, 2001;Veldhoen et al, 2014b). TCS also appears to target transcription factors (Dann and Hontela, 2011;Marlatt et al, 2013;Yueh et al, 2014). The present observation that the gene expression program can be altered at low temperature leading to a noticeable effect at permissive temperature is consistent with modulation of transcription factor status for both TCS and IBF; the associated mechanisms require further investigation.…”

Structure-Dependent Activity of Phthalate Esters and Phthalate Monoesters Binding to Human Constitutive Androstane Receptor

“…15 Triclosan can stimulate liver cell proliferation and fibrotic responses by activating CAR and therefore can accelerate hepatocellular carcinoma development, as demonstrated in a tumor promotion study in which triclosan treatment was preceded by administration of DEN in mice. 16 Ligand-elicited CAR activators such as 4-bis- [2-(3, 5-dichloropyridyloxy)] benzene can also promote DEN to induce hepatocarcinogenesis in mice. 17 These lines of evidence have increasingly confirmed that CAR regulators can activate the metabolism of some xenobiotics to induce liver turmorigenesis.…”

Up-stream mechanisms for up-regulation of miR-125b from triclosan exposure to zebrafish (Danio rerio)

“…One of these dysregulated miRNAs, miR-125b-5p, was differentially expressed in three TCS-exposure groups when compared to the control group. In cancer research, miR-125b is associated with tumor suppressor by down-regulating target oncogene (Yueh et al, 2014). Additionally, several studies have examined miR-125b in relationship to metabolic disorders in mice and humans cell lines (Zhang et al, 2015;Tili et al, 2012).…”