Activation of AH-receptor by humic substances

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Authors

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

Year of publication 2005
Type Article in Proceedings
Conference Joint Conference of Scandinavian Society of Cell Toxicology and Estonian Society of Toxicology
MU Faculty or unit

Faculty of Science

Citation
Field Environment influence on health
Keywords Humic substances; dioxin-like activity
Description Humic substances (HS) are natural compounds formed as products of decay of organic matter. They are ubiquitous in the environment, particularly in soil and aquatic ecosystems. There are generally three basic groups of humic substances: Humic acids (HA), fulvic acids and humins. Until recently, HS were generally considered to be inert in the ecosystems and the research was focused mainly on the sorption of metals and organic contaminants on HS. However, in last years the scientific concern shifted also to toxicological effects of pure humic substances. Recent studies showed that they are able to elicit hormone-like effects and changes in biochemical parameters in fish, crustaceans and nematodes. Moreover, HS seem to play an important role in progression of endemic Kashin-Beck and Blackfoot diseases. In our study, we investigated interactions between HA and Ah-receptor (receptor connected with so-called dioxin-like toxicity; AhR). We tested alkali solution of a commercially available humic acid (Fluka) and its organic extract using rat hepatoma H4IIE.luc cell line stably transfected with luciferase under control of Ah-receptor. Our results showed that both alkali solution and its organic extract elicited a significant dioxin-like activity. Chemical analysis of 16 EPA priority PAHs revealed that these PAHs are responsible for only about 0.1% of the total dioxin-like activity caused by HA mixture. In order to exclude contribution of persistent dioxin-like acting compounds such as polychlorinated dibenzodioxins/furans and PCBs we measured also activity of extract treated with H2SO4 that depletes non-persistent compounds. This extract did not activate luciferase expression at all. The dioxin-like activity was also not caused by known activators of AhR but by humic acids or their fragments. The determined REP of this humic acid was 6.10-7 which could suggest - along with high concentrations of HS in the environment a high contribution of HA to AhR-mediated toxicity. Testing of other 11 HS provided diverse results revealing relatively high dioxin-like activity for some substances and, contrary, no observed AhR-activity for others.
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