Humic Acids as Potential Activators of the Aryl Hydrocarbon Receptor

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Authors

BITTNER Michal JANOŠEK Jaroslav BLÁHA Luděk HILSCHEROVÁ Klára HOLOUBEK Ivan GIESY John Paul

Year of publication 2004
Type Article in Proceedings
Conference First Biennial Central & Eastern European Environmental Health Conference
MU Faculty or unit

Faculty of Science

Citation
Field Environment influence on health
Keywords Humic acids; AhR
Description Pure humic substances (HS) are generally regarded to be inert in ecosystems. Ecotoxicological function of HS in environment is often discussed in connection with the sorption of heavy metals and various organic xenobiotics, consequently decreasing their bioavailability and toxicity. But there were published some studies that HS can probably induce direct adverse effect on human health. That is discussed with connection to endemic appearance of Black foot disease and Kashin-Becks disease in some areas in China and Taiwan. Some experiments showed that oxidative stress caused by HS leads to damage of erythrocytes and fragmentation of DNA with subsequent apoptosis in chondrocytes. HS are the major components of the mixture of materials that comprise soil organic matter, and represent the major components of dissolved organic matter in waters. Chemical constitution of HS depends on the source of degraded organic materials, consequently HS comprise a variety of molecular structures and it is not possible to determine their unified molecular structure. Core of HS consists mostly of alkylaromatic, aliphatic and quinoide structures, and periphery from amino- and carboxyl acids and carbonyl-, phenyl- and hydroxyl groups. Aryl hydrocarbon receptor (AhR) is inducible ligand dependent transcription factor that mediates the biological and toxic effects of a structurally diverse range of chemicals, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (i.e. the most potent activator of AhR), but also tetrapyroles, flavonoides and indole-containing substances. Dioxin-like toxicity of HS was evaluated using reporter gene assay with stably transfected H4IIE.luc hepatoma cells with a luciferase reporter gene under the control of dioxin-responsive element. We tested three different kinds of humic acids that were isolated from peat, soil and coal. Significant potencies to induce AhR-mediated effects of all tested humic acids were observed. Our preliminary results suggest that HS could activate AhR and cause subsequent effects. The research was supported by the Grant Agency of the Czech Republic, No. 525/03/0367.
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