American Chemical Society
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Aryl Hydrocarbon Receptor-Mediated Effects of Chlorinated Polycyclic Aromatic Hydrocarbons

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journal contribution
posted on 2007-09-17, 00:00 authored by Takeshi Ohura, Maki Morita, Masakazu Makino, Takashi Amagai, Kayoko Shimoi
Chlorinated polycyclic aromatic hydrocarbons (ClPAHs) with 3–5 rings are ubiquitous environmental contaminants. However, toxicities of ClPAHs remain unclear. In this study, aryl hydrocarbon receptor (AhR)-mediated activities of ClPAHs were investigated by using a yeast assay system. All environmentally relevant 18 ClPAHs showed the AhR activities in the test; the activities were elevated with the number of chlorine atoms on the lower molecular weight PAH (∼three-ring and fluoranthene derivatives) but not for higher molecular weight ClPAHs (>four-ring). The similar trends were also observed in certain ClPAHs-induced cytochrome P450 1A1 expression in MCF-7 cells. The structure–activity relationship between the AhR activity and the corresponding solvent accessible surface area of ClPAHs revealed a parabolic relationship, with approximately 350 Å2/molecule as the optimal dimensions as the ligand for binding to AhR. These findings indicate that the spatial dimensions of ClPAHs apparently influence their ability to activate the AhR. Finally, we discussed the toxicity of exposure to ClPAHs based on the AhR activities, estimated that it would be approximately 30–50 times higher than that of dioxins.