Antiestrogenic Activity of Extracts of Diesel Exhaust Particulate Matter in MCF-7 Human Breast Carcinoma Cells

Abstract

Diesel exhaust particulate matter (DEP) was collected from three commercial diesel engine vehicles and DEP extracts (DEPEs) were prepared from each. The estrogenic and antiestrogenic activities of the DEPE samples were examined using an estrogen response element (ERE)-driven luciferase reporter gene assay in MCF-7 human breast cancer cells. While DEPE samples did not exhibit significant estrogen agonist activity alone, they suppressed 17 g -estradiol (E 2 )-induced luciferase activity without decreasing cell viability. Several polycyclic aromatic hydrocarbons (PAHs) acting as aryl hydrocarbon receptor (AhR) agonists were detected in the DEPEs and their concentrations were higher in DEPE samples with higher antiestrogenic activity. DEPE samples elevated cytochrome P450 (CYP) 1A1 activity. f -Naphthoflavone, an AhR antagonist, and SKF-525A, a nonselective CYP inhibitor, reversed and enhanced the antiestrogenic activity of DEPE samples, respectively. These results demonstrate that DEPE has antiestrogenic activity and this effect is primarily due to the PAH constituents acting as AhR agonists.