Interaction of Hydroxylated Polycyclic Aromatic Hydrocarbons to Estrogen Receptor

Binding activities and estrogenic/antiestrogenic activities of polycyclic aromatic hydrocarbons (PAHs) and hydroxylated PAHs (OHPAHs) having 2 to 6 rings were evaluated by competition assay and yeast two-hybrid assay expressing human estrogen receptor (hER), respectively. PAHs did not bind to hER and did not show any activity. On the other hand, OHPAHs bound to hER and several OHPAHs showed estrogenic or antiestrogenic activity. Relative estrogenic activity (REP E ) and antiestrogenic activity (REP AE ) were calculated from the values of E 2 and 4-hydroxytamoxyfen as positive controls, respectively. Several OHPAHs having 4 rings showed strongly estrogenic activity. 4-Hydroxybenzo[a]anthracene exhibited the strongest estrogenic activity (REP E = 7.5 × 10−3 ) followed by 3-hydroxybenzo[a]anthracene and 2-hydroxychrysene (REP E = 4.2 × 10−3 ). Several other 4-ring OHPAHs showed strongly antiestrogenic activity. 3-Hydroxybenzo[c]phenanthrene exhibited the strongest antiestrogenic activity (REP AE = 190) followed by 2-hydroxybenzo[c]phenanthrene (REP AE = 69) and 2- hydroxybenz [a]anthracene (REP AE = 0.42). The results suggested that there is a strong structure – activity relationship.