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Proc Natl Acad Sci U S A. 2014 Dec 2;111(48):17200-5. doi: 10.1073/pnas.1419119111. Epub 2014 Nov 17.

The commonly used antimicrobial additive triclosan is a liver tumor promoter.

Author information

1
Laboratory of Environmental Toxicology, Departments of Chemistry & Biochemistry and Pharmacology, and.
2
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093;
3
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037; and.
4
Department of Entomology and Nematology and Comprehensive Cancer Center, University of California Davis Cancer Center, University of California, Davis, CA 95616 rtukey@ucsd.edu bdhammock@ucdavis.edu.
5
Laboratory of Environmental Toxicology, Departments of Chemistry & Biochemistry and Pharmacology, and rtukey@ucsd.edu bdhammock@ucdavis.edu.

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) and, 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. TCS-mediated 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.

KEYWORDS:

hepatocellular carcinoma; liver fibrosis; triclosan; tumor promoter

PMID:
25404284
PMCID:
PMC4260592
DOI:
10.1073/pnas.1419119111
[Indexed for MEDLINE]
Free PMC Article

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