Aryl Hydrocarbon Receptor-Mediated Gene Expression by Chlorinated Polycyclic Aromatic Hydrocarbons and Cross-Talk with Estrogen Receptors

Chlorinated polycyclic aromatic hydrocarbons (ClPAHs) have been recently reported to occur widely in environmental matrices such as urban air, vehicle exhaust, snow, tap water and sediments. However, toxicological information on ClPAHs is currently very limited. Therefore, in the present study, we evaluated the influence of typical ClPAHs like chlorinated phenanthrenes (ClPhes), chlorinated pyrene (ClPy) and chlorinated benzo[a]pyrene (ClBaP), on the induction of aryl hydrocarbon receptor (AhR)mediated cytochrome P-450 (CYP) 1A1 and also estrogen receptors (ERs)mediated cathepsin D mRNA using MCF-7 human breast cancer cells. Expressions of CYP1A1 and catepsin D were measured upon treatment of 2 μM of each chemical, using quantitative RT-PCR system after incubation at 37°C for 12 hr. Phe did not induce any expression of CYP1A1 mRNA. On the other hand, mono-, di-, and tri-ClPhe increased these expressions with respect to the number of chlorine atoms on the Phe skeleton. ClBaP also induced CYP1A1 at the same levels as in the case of the parent chemical BaP. Py and ClPy did not induce any change. Other AhR activated ligands, such as 3-methylcholanthrene, have been reported to have AhR-ERs cross-talk activity. However, tri-ClPhe didn’t stimulate this cross-talk pathway. These results indicate that estrogenic action mediated ERs signaling through AhR activation does not necessarily occur in all AhR avtivated lignads.