Triclocarban mediates induction of xenobiotic metabolism through activation of the constitutive androstane receptor and the estrogen receptor alpha

Mei Fei Yueh, Tao Li, Ronald M. Evans, Bruce Hammock, Robert H. Tukey

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Triclocarban (3,4,4′-trichlorocarbanilide, TCC) is used as a broad-based antimicrobial agent that is commonly added to personal hygiene products. Because of its extensive use in the health care industry and resistance to degradation in sewage treatment processes, TCC has become a significant waste product that is found in numerous environmental compartments where humans and wildlife can be exposed. While TCC has been linked to a range of health and environmental effects, few studies have been conducted linking exposure to TCC and induction of xenobiotic metabolism through regulation by environmental sensors such as the nuclear xenobiotic receptors (XenoRs). To identify the ability of TCC to activate xenobiotic sensors, we monitored XenoR activities in response to TCC treatment using luciferase-based reporter assays. Among the XenoRs in the reporter screening assay, TCC promotes both constitutive androstane receptor (CAR) and estrogen receptor alpha (ERα) activities. TCC treatment to hUGT1 mice resulted in induction of the UGT1A genes in liver. This induction was dependent upon the constitutive active/androstane receptor (CAR) because no induction occurred in hUGT1Car-/- mice. Induction of the UGT1A genes by TCC corresponded with induction of Cyp2b10, another CAR target gene. TCC was demonstrated to be a phenobarbital-like activator of CAR in receptor-based assays. While it has been suggested that TCC be classified as an endocrine disruptor, it activates ERα leading to induction of Cyp1b1 in female ovaries as well as in promoter activity. Activation of ERα by TCC in receptor-based assays also promotes induction of human CYP2B6. These observations demonstrate that TCC activates nuclear xenobiotic receptors CAR and ERα both in vivo and in vitro and might have the potential to alter normal physiological homeostasis. Activation of these xenobiotic-sensing receptors amplifies gene expression profiles that might represent a mechanistic base for potential human health effects from exposure to TCC.

Original languageEnglish (US)
Article numbere37705
JournalPLoS One
Volume7
Issue number6
DOIs
StatePublished - Jun 15 2012

Fingerprint

Estrogen Receptor alpha
Xenobiotics
xenobiotics
Metabolism
Chemical activation
receptors
metabolism
Assays
gene induction
assays
Genes
constitutive androstane receptor
triclocarban
estrogen receptors
Cytoplasmic and Nuclear Receptors
phenobarbital
endocrine-disrupting chemicals
sewage treatment
mice
Health

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Triclocarban mediates induction of xenobiotic metabolism through activation of the constitutive androstane receptor and the estrogen receptor alpha. / Yueh, Mei Fei; Li, Tao; Evans, Ronald M.; Hammock, Bruce; Tukey, Robert H.

In: PLoS One, Vol. 7, No. 6, e37705, 15.06.2012.

Research output: Contribution to journalArticle

Yueh, Mei Fei ; Li, Tao ; Evans, Ronald M. ; Hammock, Bruce ; Tukey, Robert H. / Triclocarban mediates induction of xenobiotic metabolism through activation of the constitutive androstane receptor and the estrogen receptor alpha. In: PLoS One. 2012 ; Vol. 7, No. 6.
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