Aryl hydrocarbon receptor-mediated effects of chlorinated polycyclic aromatic hydrocarbons

Chlorinated polycyclic aromatic hydrocarbons (CIPAHs) with 3-5 rings are ubiquitous environmental contaminants. However, toxicities of CIPAHs remain unclear. In this study, aryl hydrocarbon receptor (AhR)-mediated activities of CIPAHs were investigated by using a yeast assay system. All environmentally relevant 18 CIPAHs showed the AhR activities in the test; the activities were elevated with the number of chlorine atoms on the lower molecular weight PAH (similar to three-ring and fluoranthene derivatives) but not for higher molecular weight CIPAHs (>four-ring). The similar trends were also observed in certain CIPAHs-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 CIPAHs revealed a parabolic relationship, with approximately 350 A (2)/molecule as the optimal dimensions as the ligand for binding to AhR. These findings indicate that the spatial dimensions of CIPAHs apparently influence their ability to activate the AhR. Finally, we discussed the toxicity of exposure to CIPAHs based on the AhR activities, estimated that it would be approximately 30-50 times higher than that of dioxins.