The commonly used antimicrobial additive triclosan is a liver tumor promoter

Mei Fei Yueha, Koji Taniguchib, Shujuan Chena, Ronald M. Evansc, Bruce D. Hammockd, Michael Karinb, Robert H. Tukeya

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

Triclosan [5-chloro-2-(2,4-dichlorophenoxy)phenol; TCS] is a synthetic, broad-spectrum antibacterial chemical used in a wide range of consumer products including soaps, cosmetics, therapeutics, and plastics. The general population is exposed to TCS because of its prevalence in a variety of daily care products as well as through waterborne contamination. TCS is linked to a multitude of health and environmental effects, ranging from endocrine disruption and impaired muscle contraction to effects on aquatic ecosystems. We discovered that TCS was capable of stimulating liver cell proliferation and fibrotic responses, accompanied by signs of oxidative stress. Through a reporter screening assay with an array of nuclear xenobiotic receptors (XenoRs), we found that TCS activates the nuclear receptor constitutive androstane receptor (CAR), contrary to previous reports, has no significant effect on mouse peroxisome proliferation activating receptor α (PPARα). Using the procarcinogen diethylnitrosamine (DEN) to initiate tumorigenesis in mice, we discovered that TCS substantially accelerates hepatocellular carcinoma (HCC) development, acting as a liver tumor promoter. TCS-treated mice exhibited a large increase in tumor multiplicity, size, and incidence compared with control mice. TCSmediated liver regeneration and fibrosis preceded HCC development and may constitute the primary tumor-promoting mechanism through which TCS acts. These findings strongly suggest there are adverse health effects in mice with long-term TCS exposure, especially on enhancing liver fibrogenesis and tumorigenesis, and the relevance of TCS liver toxicity to humans should be evaluated.

Original languageEnglish (US)
Pages (from-to)17200-17205
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number48
DOIs
StatePublished - Nov 17 2014

Keywords

  • Hepatocellular carcinoma
  • Liver fibrosis
  • Triclosan
  • Tumor promoter

ASJC Scopus subject areas

  • General

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    Yueha, M. F., Taniguchib, K., Chena, S., Evansc, R. M., Hammockd, B. D., Karinb, M., & Tukeya, R. H. (2014). The commonly used antimicrobial additive triclosan is a liver tumor promoter. Proceedings of the National Academy of Sciences of the United States of America, 111(48), 17200-17205. https://doi.org/10.1073/pnas.1419119111