Activation of aryl hydrocarbon receptor signaling by extracts of teak and other wood dusts

Environ Toxicol. 2015 Dec;30(12):1375-84. doi: 10.1002/tox.22007. Epub 2014 Jun 5.

Abstract

Wood dusts, as a group, are categorized as known human carcinogens, but the risks of exposure to specific types of wood dusts and the carcinogenic chemicals they contain are not well studied. Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is linked to the carcinogenic action of specific classes of chemicals. Here we examined whether chemicals in various wood dusts had the potential to activate AhR signaling as a potential toxic mechanism of action. We found that methanol extracts of teak, walnut, mahogany, and poplar dusts contained a wide range of AhR ligand activity, whereas extracts of oak, pine, and other softwoods did not contain appreciable activity. Teak dust extract, being particularly potent, was subjected to chemical analysis. The 2-methylanthraquinone (2-MAQ) accounted for the AhR ligand activity and was present at an average concentration of 0.27 parts per hundred in teak dust. Pure 2-MAQ potently induced AhR signaling (EC50 115 nM), confirming that this was the active ligand. Aqueous extracts of teak dust made using yeast or mammalian cell culture medium also contained robust AhR activity, suggesting the 2-MAQ ligand is soluble at bioactive concentrations in physiologically relevant fluids. The high concentration and potency of 2-MAQ in teak wood suggest it may mediate toxic effects through activation of AhR signaling in exposed wood workers.

Keywords: 2-methylanthraquinone; aryl hydrocarbon receptor; sinonasal cancer; teak; wood dust.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anthraquinones / chemistry
  • Anthraquinones / toxicity
  • Cytochrome P-450 CYP1A1 / genetics
  • Cytochrome P-450 CYP1A1 / metabolism
  • Dust / analysis*
  • Gene Expression Regulation
  • Hep G2 Cells
  • Humans
  • Methanol / chemistry
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Signal Transduction / drug effects
  • Wood / chemistry*

Substances

  • Anthraquinones
  • Dust
  • Receptors, Aryl Hydrocarbon
  • Cytochrome P-450 CYP1A1
  • 2-methylanthraquinone
  • Methanol