Wilson Mark J, Sabbioni Gabriele, Rando Roy, Miller Charles A
Department of Global Environmental Health Sciences, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, 70112.
Environ Toxicol. 2015 Dec;30(12):1375-84. doi: 10.1002/tox.22007. Epub 2014 Jun 5.
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.
作为一个类别,木尘被归类为已知的人类致癌物,但对于接触特定类型木尘及其所含致癌化学物质的风险,尚未进行充分研究。芳烃受体(AhR)是一种配体激活的转录因子,与特定类别的化学物质的致癌作用有关。在这里,我们研究了各种木尘中的化学物质是否有可能激活AhR信号通路,将其作为一种潜在的毒性作用机制。我们发现柚木、核桃木、桃花心木和杨木尘的甲醇提取物具有广泛的AhR配体活性,而橡木、松木和其他软木的提取物则没有明显活性。柚木尘提取物活性特别强,因此对其进行了化学分析。2-甲基蒽醌(2-MAQ)是AhR配体活性的来源,在柚木尘中的平均浓度为千分之0.27。纯2-MAQ能有效诱导AhR信号通路(半数有效浓度为115 nM),证实其为活性配体。使用酵母或哺乳动物细胞培养基制备的柚木尘水提取物也具有较强的AhR活性,这表明2-MAQ配体在生理相关液体中以生物活性浓度可溶。柚木中2-MAQ的高浓度和高效性表明,它可能通过激活暴露的木材工人的AhR信号通路来介导毒性作用。